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Keywords: beta blockers; multiple myeloma; pomalidomide; progression-free survival EN beta blockers multiple myeloma pomalidomide progression-free survival 433 436 4 02/13/21 20210301 NES 210301 There is emerging evidences in recent years to suggest antitumor benefits of beta blockers (BB). The patients were further categorized into four groups based on their medication intake during the POM trial: (a) no cardiac or antihypertensive medications (n = 119); (b) BB alone (n = 29); (c) other non-BB cardiac or antihypertensive agents (n = 35); (d) both BB and non-BB medications (n = 25). GLO:8DW/01mar21:ejh13559-fig-0001.jpg PHOTO (COLOR): 1 Beta blocker (BB) intake significantly improves progression-free survival (PFS) and overall survival (OS) in myeloma patients treated with pomalidomide. [Extracted from the article]

Background: Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival.Methods: Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis.Results: Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01).Conclusions: Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

This spotlight review focuses on the second-generation immunomodulatory drug pomalidomide, which was recently approved by the US Food and Drug Administration. This drug was approved for patients with multiple myeloma who have received at least 2 prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of the last therapy. This review focuses on the clinical trial data that led to approval and provides advice for treating physicians who are now prescribing this drug for patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Early versus delayed autologous stem cell transplantation (SCT) results in comparable overall survival in patients with multiple myeloma (MM) who receive alkylator-based therapies. It is not clear whether this paradigm holds true in the context of new therapies, such as immunomodulatory drugs (IMiDs). METHODS: The authors studied 290 patients with untreated MM who received IMiD-based initial therapy, including 123 patients who received thalidomide-dexamethasone (TD) and 167 patients who received lenalidomide-dexamethasone (LD) induction before SCT. Patients who underwent a stem cell harvest attempt were considered transplantation-eligible and were included. SCT within 12 months of diagnosis and within 2 months of harvest were considered early SCT (n = 173; 60%). SCT >12 months after diagnosis was considered delayed SCT (n = 112; 40%). RESULTS: In the delayed SCT group, 42 patients had undergone SCT at the time of the current report, and the median estimated time to SCT was 5.3 months and 44.5 months in the early SCT and delayed SCT groups, respectively. The 4-year overall survival rate from diagnosis was 73% in both groups ( P = .3) and was comparable in those who received TD (68% vs 64%, respectively) and those who received LD (82% vs 86%, respectively) as initial therapy. The time to progression after SCT was similar between the early and delayed SCT groups (20 months vs 16 months; P value nonsignificant). CONCLUSIONS: The current results indicated that, in transplantation-eligible patients who receive IMiDs as initial therapy followed by early stem cell mobilization, delayed SCT results in similar overall survival compared with early SCT. It is noteworthy that an excellent 4-year survival rate of >80% was observed among transplantation-eligible patients who received initial therapy with LD regardless of the timing of transplantation. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using the pomalidomide with weekly dexamethasone (Pom/dex) regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Pomalidomide was given orally 2 or 4 mg daily with dexamethasone 40 mg weekly. Thirty-five patients were enrolled in each cohort. Confirmed responses in the 2-mg cohort consisted of very good partial response (VGPR) in 5 (14%), partial response (PR) in 4 (11%), minor response (MR) in 8 (23%) for an overall response rate of 49%. In the 4-mg cohort, confirmed responses consisted of complete response (CR) in 1 (3%), VGPR in 3 (9%), PR in 6 (17%), MR in 5 (14%) for an overall response rate of 43%. Overall survival at 6 months is 78% and 67% in the 2- and 4-mg cohort, respectively. Myelosuppression was the most common toxicity. This nonrandomized data suggests no advantage for 4 mg over the 2 mg daily. Pomalidomide overcomes resistance in myeloma refractory to both lenalidomide and bortezomib. [ABSTRACT FROM AUTHOR]

Thalidomide possesses potent anti-inflammatory, immunomodulatory, and antiangiogenic properties. Thalidomide combined with corticosteroids is therapeutically active in multiple myeloma and myelofibrosis (MF). Lenalidomide and pomalidomide are second-generation immunomodulatory drugs (IMiDs) that were created by chemical modification of thalidomide with the intent to reduce toxicity and enhance therapeutic activity. Both drugs have also been shown to be active in the treatment of myeloma and MF. Thalidomide is US Food and Drug Administration (FDA)-approved for use in acute erythema nodosum leprosum and, in combination with dexamethasone, in newly diagnosed myeloma. Lenalidomide is approved for use in low/intermediate-1 risk myelodysplastic syndromes associated with transfusion-dependent anemia and a deletion 5q cytogenetic abnormality and, in combination with dexamethasone, in relapsed myeloma. Pomalidomide is currently not FDA-approved. Herein, we summarize what is currently known about the biologic and therapeutic effects of pomalidomide. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy for the management of immunoglobulin light chain amyloidosis remains an effective and viable treatment technique for selected patients with this disorder. We reviewed the medical records of 434 patients uniformly treated with high-dose chemotherapy and autologous stem cell transplant at Mayo Clinic, Rochester, Minnesota, between 8 March 1996 and 13 April 2010. Outcomes, engraftment, and predictors of early mortality were reviewed. Median survival has not been reached for the patients with a complete response, is 107 months for those with a partial response, and is 32 months for patients with no response ( p < 0.001). The only predictor of survival was cardiac stage ( p < 0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival. [ABSTRACT FROM AUTHOR]

Abstract: The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial of interleukin-12 (IL-12) for plateau phase multiple myeloma. Patients were initially treated with IL-12 250ng/kg I.V. daily for 5 days every 3 weeks. The trial was modified due to toxicity after the first 16 patients. IL-12 was given 300ng/kg subcutaneously twice weekly for 24 weeks. Of 48 eligible patients, there were 4 objective responses (8.3%), all CR. The median survival and progression-free survival were 42.8 and 11.4 months. Unacceptable grade 3 or 4 non-hematologic toxicity (31% with IL-12 subcutaneously and 63% with IL-12 intravenously) was observed. [Copyright &y& Elsevier]

OBJECTIVE: To conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or Indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma. PATIENTS AND METHODS: Stromal cells were cocultured with IL-Iβ-expressing myeloma cells In the presence of dexamethasone, IL-1 receptor antagonist (IL-1Ra), or both. Levels of lnterieukin 6 (IL-6) and of apoptosis were also quantified. Between November 19, 2002, and May 24, 2007, 47 patients were enrolled in the study and subsequently treated with IL-1Ra. in 25(53%) of the 47 study patients, low-dose dexamethasone (20 mg/wk) was added. The primary end point was progression-free survival (PFS). RESULTS: In vitro, IL-1Ra was superior to dexamethasone at Inhibiting IL-6 production; maximal IL-6 inhibition and apoptosis Induction were achieved by addition of both IL-1Ra and dexamethasone. In the clinical trial, 3 patients achieved a minor response to IL-1Ra alone; 5 patIents achieved a partial response and 4 patients a minor response after addition of dexamethasone. Seven patients showed a decrease In the plasma cell labeling Index that paralleled a decrease In high-sensitivity C-reactive protein (hs-CRP) levels. The median overall PFS was 37.5 months. The median PFS for patients without (n=12) or with (n=35) a greater than 15% decrease In 6-month vs baseline hs-CRP levels was 6 months and more than 3 years, respectively (P=.002). Disease stability was maintained in 8 patients who received therapy for more than 4 years. CONCLUSION: In patients with smoldering or indolent multiple myeloma who were at risk of progression to active myeloma, treatment with IL-1 inhibitors decreased the myeloma proliferative rate and hs-CRP levels in those who responded, leading to a chronic disease state and an Improved PFS. [ABSTRACT FROM AUTHOR]

Background: Historically, patients with AL amyloidosis and overt congestive heart failure have had an ominous prognosis with median survival of approximately 6 months. Methods: Between 1994 and 2005, 11 patients underwent sequential orthotopic heart transplantation (HT) followed by autologous peripheral blood stem cell transplantation (SCT) for treatment of AL amyloidosis. Patients were accepted for this approach if they had heart-dominant AL with minimal/no other organ impairment and no evidence of multiple myeloma. Conditioning chemotherapy consisted of melphalan 200 mg/m2 (6 patients) or melphalan 140 mg/m2 (5 patients). Results: Two patients died of complications from the SCT (18% transplant-related mortality). Nine patients survived both the HT and the SCT. Three patients subsequently died from progressive amyloidosis at 66, 56.7 and 55 months after SCT. The 1- and 5-year survival for HT was 82% and 65%. The median survival was 76 months from HT and 57 months from SCT. Conclusions: These data suggest that aggressive treatment of the underlying plasma cell clone after HT may improve long-term outcomes in patients with cardiac amyloid. HT followed by SCT is feasible and offers the possibility of remission for carefully selected patients with cardiac amyloidosis. [Copyright &y& Elsevier]

Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis and high vascular endothelial growth factor (VEGF). High-dose chemotherapy with autologous peripheral blood stem cell transplantation (ASCT) ultimately yields excellent clinical responses, but there can be considerable peritransplant morbidity. We have treated 30 POEMS patients with ASCT at Mayo Clinic, Rochester. During transplant period, patients had high rates of fever, diarrhea, weight gain and rash (93%, 77%, 53% and 43%, respectively). Only 13% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0–175). Splenomegaly was the baseline factor that best predicted for a complicated peritransplant course. Depending on the definition used, ∼50% of patients satisfied criteria for engraftment syndrome. Earlier and more aggressive use of corticosteroids may be associated with less complicated post-transplant courses. Median overall survival has not been reached; the treatment-related mortality was 3%. In addition, important clinical improvements and reductions in plasma VEGF levels can occur in the absence of significant decrease in the monoclonal protein. Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the long-term effects of a combined regimen of lenalldomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma. PATIENTS AND METHODS: From March 2004 through October 2004, 34 patients were registered for the study. They were treated with 25 mg/d of lenalidomide on days 1 through 21 of a 28-day cycle and 40 mg/d of dexamethasone on days 1 through 4, 9 through 12, and 17 through 20 of each cycle. After 4 cycles of therapy, patients were allowed to discontinue treatment to pursue autologous stem cell transplant (SCT). Treatment beyond 4 cycles was permitted at the physician's discretion. RESULTS: Thirteen patients proceeded to SCT after initial therapy and were censored at that time point for purposes of calculation of response. Thirty-one patients achieved an objective response, defined as a partial response or better (91%; 95% confidence interval, 79%-98%), with a complete response plus very good partial response rate of 56%. The complete response plus very good partial response among the 21 patients who received Rev-Dex without SCT was 67%. The 2-year progression-free survival rates for patients proceeding to SCT and patients remaining on Rev-Dex were 83% and 59%, respectively; the OS rates were 92% and 90% at 2 years and 92% and 85% at 3 years, respectively. The 3-year OS rate for the whole cohort was 88%. CONCLUSION: The Rev-Dex regimen is highly active in the treatment of newly diagnosed multiple myeloma. Responses are durable with a low progression rate at 2 years. Randomized trials that incorporate quality-of-life measures are needed to determine if this and other combination regimens are better used early in therapy or should be reserved for later interventions. [ABSTRACT FROM AUTHOR]

Bisphosphonates are effective in the prevention and treatment of bone disease in multiple myeloma (MM). Osteonecrosis of the jaw is increasingly recognized as a serious complication of long-term bisphosphonate therapy. issues such as the choice of bisphosphonate and duration of therapy have become the subject of intense debate given patient safety concerns. We reviewed available data concerning the use of bisphosphonates in MM. Guidelines for the use of bisphosphonates in MM were developed by a multidisciplinary panel consisting of hematologists, dental specialists, and nurses specializing in the treatment of MM. We conclude that intravenous pamidronate and intravenous zoledronic acid are equally effective and superior to placebo in reducing skeletal complications. Pamidronate is favored over zoledronic acid until more data are available on the risk of complications (osteonecrosis of the Jaw). We recommend discontinuing bisphosphonates after 2 years of therapy for patients who achieve complete response and/or plateau phase. For patients whose disease is active, who have not achieved a response, or who have threatening bone disease beyond 2 years, therapy can be decreased to every 3 months. These guidelines were developed in the interest of patient safety and will be reexamined as new data emerge regarding risks and benefits. [ABSTRACT FROM AUTHOR]

To determine the natural history of thromboembolism in patients with biopsy-proven AL amyloidosis, medical records of 2,132 patients evaluated at Mayo Clinic between 1975 and 2000 were reviewed. Forty patients (21 male) were found to have objectively documented thromboembolism. The median age was 65 years. Four patients had a monoclonal gammopathy of undetermined significance, 20 had an unspecified plasma cell proliferative disorder, 11 had multiple myeloma, and 1 had Waldenström macroglobulinemia. Twelve patients had cardiac amyloid, and 20 had renal amyloid. Neither the extent of the amyloid nor the type of monoclonal protein was predictive of the development of thromboembolic events. Thromboembolism preceded the diagnosis of AL amyloidosis in 11 patients, occurred at the time of diagnosis or within 1 month after diagnosis in 11 patients, and occurred 1 month or more after diagnosis in 18 patients. Twenty-nine patients (73%) had venous thrombosis and 11 (28%) had arterial thrombosis. Eight patients (20%) died within 1 month after the thrombotic event, and 18 (45%) died within 1 year. The development of thrombosis in patients with AL amyloidosis appears to predict significant mortality within the first month and year after the event. [ABSTRACT FROM AUTHOR]

Pax5 is a transcription factor that is critical in the bone marrow for differentiation and proliferation of B cells until the plasma cell stage. In Pax5 −/− mice, B-cell development stalls at the pro-B-cell stage. Messenger RNA profiles of alternatively spliced isoforms of Pax5 in bone marrow frequently differ between multiple myeloma (MM) patients and healthy donors. We sought to determine if Pax5 mRNA profiles also differed in blood and unexpectedly detected the presence of a previously unreported exon that alters the amino acid code for the transactivating domain of Pax5 in CD138− B cells. This unique exon escapes detection by conventional analyses of RT-PCR products and may serve as a prototype for other exons, in other genes, that escape RT-PCR detection. Eight percent of tested human subjects were heterozygous for an allele with a nonsynonymous nucleotide substitution in the new exon, and one MM patient was homozygotic for this base difference. Subsequent analysis of plasma and B-cell populations from bone marrow revealed a markedly reduced mRNA expression of the new isoform in cells from MM patients when compared to cells from normal subjects. [ABSTRACT FROM AUTHOR]

Treatments effective against multiple myeloma may be useful in primary systemic amyloidosis (AL). Thalidomide is active in myeloma. Results of the first 12 patients enrolled on a phase 11 trial of thalidomide for AL are presented. Progressive edema, cognitive difficulties, and constipation occurred in approximately 75%; dyspnea, dizziness and rash in 50%. Five developed progressive renal insufficiency. Deep venous thrombosis and syncope each occurred in two. Median time on the study was 72 days, range was 25 to 333 days. All 12 have withdrawn from the study (side-effects, 6; progression, 4; and death, 2 patients). AL patients do not tolerate high dose thalidomide. [ABSTRACT FROM AUTHOR]

: PurposeTo review the characteristics and outcomes of amyloidosis patients treated with high-dose chemotherapy and stem cell reconstitution.: Subjects and methodsSixty-six patients with biopsy-proven amyloidosis received transplants between March 1996 and January 2001. All patients had evidence of a clonal plasma cell dyscrasia; those with nonimmunoglobulin forms of amyloidosis were excluded, as were those who had no symptoms of amyloidosis, purpura, carpal tunnel syndrome, or symptomatic multiple myeloma.: ResultsAmyloid was seen clinically in the kidneys (n = 45 patients), heart (n = 32), peripheral nerves (n = 11), and liver (n = 11). A monoclonal protein was found in the serum in 46 patients and in the urine in 57 patients. The median daily urinary protein loss was 4.1 g. Septal thickness, measured by echocardiography, ranged from 7 to 24 mm (median, 12 mm); 8 patients had a septal thickness ≥16 mm. Ten patients received transplants 1 year or more after diagnosis. All patients received melphalan-based chemotherapy; 17 patients were conditioned with total body irradiation. Nine patients required dialysis, 7 of whom died. Treatment-related mortality for stem cell transplantation was 14% (9/66). After a median of 25 months of follow-up after transplantation, the percentage of patients alive with one organ involved was 91% (31 of 34); two organs, 82% (18 of 22); three organs, 33% (3 of 9); and four organs, 0% (0 of 1). Hematologic responses were seen in 33 patients and organ responses in 32 patients. The 2-year actuarial survival of all patients was 70%.: ConclusionThe number of organs involved before stem cell transplantation for amyloidosis is the most important factor in predicting subsequent survival. Stem cell transplantation should be considered as a treatment option for selected patients with amyloidosis. [Copyright &y& Elsevier]

Immunoglobulin light chain amyloidosis and the kidney. Amyloidosis (AL) is a common cause of nephrotic syndrome in nondiabetic, nonhypertensive adults. All adult patients with nephrotic syndrome should have immunofixation of serum and urine as a screen. The finding of a monoclonal protein, particularly of lambda type, should lead to a subcutaneous fat aspirate or bone marrow biopsy to search for amyloid deposits. When the result of either test is positive, a kidney biopsy is unnecessary. The prognosis of patients who have renal amyloidosis depends on the concentration of serum creatinine at presentation and whether an echocardiographic evaluation demonstrates infiltrative cardiomyopathy. Most therapies are directed against the plasma cell dyscrasia present in all patients with AL and can include melphalan and prednisone, high-dose dexamethasone, and, most recently, peripheral blood stem cell transplantation. [ABSTRACT FROM AUTHOR]

The article discusses two different study on the use of dexamethasone and pomalidomide in patients with relapsed and refractory multiple myeloma (MM). It says that P. G. Richardson and colleagues report their phase 1 dose-escalation study to identify pomalidomide maximum tolerated dose (MTD) in patients. It mentions that X. Leleu and colleagues describe their randomized phase 2 study which compares different schedules of polamidomide dosing.

The efficacy of retreatment with immunomodulatory drugs (IMiDs) among patients with multiple myeloma who received this class of drugs for initial therapy is unknown. We studied 140 patients who received either thalidomide-dexamethasone (81; 58%) or lenalidomide-dexamethasone (59; 42%) as first-line therapy of multiple myeloma followed by repeat IMiD (thalidomide [34; 24%] or lenalidomide [106; 76%]) as one of the salvage regimens. A median of 2 treatments (range, 1-6), including a stem cell transplant in 105 patients (75%), were administered before IMiD-based salvage therapy. The median time from diagnosis to repeat exposure to IMiD was 28 months. Among the 113 evaluable patients, 50 (44%) achieved at least a partial response, and 63 (56%) achieved less than a partial response to repeat IMiD. Response rates with lenalidomide retreatment were higher than with repeat administration of thalidomide. [ABSTRACT FROM AUTHOR]

The article focuses on the development concerning treatment of multiple myeloma. Along with the development is the emergence of new combination regimens in treating the disease. Some of the combination therapies are the pegylated liposomal doxorubicin, vincristine and decreased-frequency dexamethasone with thalidomide. Moreover, these new combination therapies have shown to be effective in treating the disease.

Summary: Improvement in survival in Light chain (AL) amyloidosis has been seen over recent decades, enabling more patients to achieve long‐term survival. Patients with AL amyloidosis who survived ≥10 years from time of diagnosis (n = 186) were the subject of this study. Ten‐year survivors represented 22% of the total population. These patients were characterized by favourable patient, organ and plasma cell features. Of note, trisomies were less common among 10‐year survivors compared to those who did not survive to 10 years. All‐time best haematological response was complete response in 67%, very good partial response in 30%, partial response in 2% and no response in 1%, with 11% having received a consolidative strategy for inadequate response to first line therapy. The overall organ response rate to first‐line therapy was 76%, which increased to 86% when considering subsequent line(s) of therapy. Forty‐seven percent of the 10‐year survivors did not require a second‐line therapy. The median treatment‐free survival (TFS) among the 10‐year survivors was 10·5 years (interquartile range 7·4‐12·2). On multivariate analysis independent predictors for TFS were the achievement of complete haematological response and lack of cardiac involvement. Long‐term survivors are increasingly seen in AL amyloidosis and present distinct patient, organ and clonal disease features. [ABSTRACT FROM AUTHOR]

The current treatment paradigm of AL amyloidosis lacks effective fibril-directed therapies. Doxycycline has been shown to have anti-fibril properties in preclinical models. In 2012, we reported that posttransplant prophylaxis with doxycycline was associated with improved survival compared to penicillin in patients with haematologic response. We provide here updated results after long-term follow up. We included 553 patients who underwent transplant between July 24th, 1996, and June 24th, 2014. Doxycycline 100 mg daily was used for prophylaxis in patients with penicillin allergy; since 2013, doxycycline was used as the standard for prophylaxis. Prophylaxis was typically continued for a year after transplant. The median follow-up from transplant was 12.7 years. Doxycycline was used for prophylaxis in 33% of patients; the rest received penicillin. The median time to next treatment was 6.0 (95%CI; 4.4–8.8) years and 6.0 (95%CI; 4.9–7.1) years in the doxycycline and penicillin groups, respectively (p =.89). The median overall survival was 12.0 (95%CI: 11.0–19.6) years and 11.0 (95%CI: 9.6–12.7) years in the 2 groups, respectively (p =.17). There was a minimal trend towards improved survival with doxycycline among patients with ≥ very good partial response and among patients with organ response that was not statistically significant. After long-term follow-up, there is no clear evidence to support benefit of doxycycline in the post-transplant setting. [ABSTRACT FROM AUTHOR]

In this article the authors discuss the article "Salvage Autologous Stem Cell Transplant for Multiple Myeloma Relapsing or Progressing After Upfront Autologous Transplant" by H. W. Auner et al. They are supportive of several points which are raised in Auner et al.'s article and of using autologous stem cell transplantation in patients with multiple myeloma.

A response by M. Q. Lacy, A. Dispenzieri, M. A. Gertz and colleagues to a letter to the editor about their article "Mayo Clinic consensus statement for the use of bisphosphonates in multiple myeloma."

The significance of serum lactate dehydrogenase ( LDH) in light chain ( AL) amyloidosis has not been previously explored. We studied 1019 newly diagnosed patients and correlated the elevation of LDH above the upper limit of normal ( ULN) with disease characteristics and outcome. Four hundred and nine patients had an LDH above ULN, representing 40% of the study population. Patients with an elevated LDH were older, were less likely to be male and had more extensive organ involvement compared to patients with a normal LDH. Patients with high LDH had greater cardiac and renal dysfunction. Elevated LDH was an independent prognostic marker for overall survival and for death within 6 months of diagnosis, but this was restricted to patients not eligible for stem cell transplant. Serum LDH may act as a marker for organ damage and should be explored as a potential marker for tissue healing and organ recovery. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia increases with age and is associated with poor survival outcomes in patients with cancer. By using a deep learning–based segmentation approach, clinical computed tomography (CT) images of the abdomen of patients with newly diagnosed multiple myeloma (NDMM) were reviewed to determine whether the presence of sarcopenia had any prognostic value. Methods: Sarcopenia was detected by accurate segmentation and measurement of the skeletal muscle components present at the level of the L3 vertebrae. These skeletal muscle measurements were further normalized by the height of the patient to obtain the skeletal muscle index for each patient to classify them as sarcopenic or not. Results: The study cohort consisted of 322 patients of which 67 (28%) were categorized as having high risk (HR) fluorescence in situ hybridization (FISH) cytogenetics. A total of 171 (53%) patients were sarcopenic based on their peri‐diagnosis standard‐dose CT scan. The median overall survival (OS) and 2‐year mortality rate for sarcopenic patients was 44 months and 40% compared to 90 months and 18% for those not sarcopenic, respectively (p <.0001 for both comparisons). In a multivariable model, the adverse prognostic impact of sarcopenia was independent of International Staging System stage, age, and HR FISH cytogenetics. Conclusions: Sarcopenia identified by a machine learning–based convolutional neural network algorithm significantly affects OS in patients with NDMM. Future studies using this machine learning–based methodology of assessing sarcopenia in larger prospective clinical trials are required to validate these findings. A deep learning–based algorithm was used to identify sarcopenia in abdominal computed tomography images of patients with newly diagnosed myeloma. The presence of sarcopenia was independently prognostic for survival in newly diagnosed multiple myeloma patients even after accounting for conventional prognostic factors. [ABSTRACT FROM AUTHOR]

Considerable healthcare resource utilization and financial burden have been associated with the treatment of WM; however, the impact of health insurance status on outcomes has not been previously reported. We conducted a National Cancer Database analysis of newly diagnosed cases of active WM between 2004 and 2017 to evaluate the impact of insurance status on outcomes. For patients <65 years old (n = 1249, male sex: 62.4%, median age: 58 years), significant insurance-based survival differences were observed on multivariable analysis; patients who were uninsured [n = 63; HR 3.11 (95%CI, 1.77–5.45), p < 0.001], on Medicaid [n = 87; HR 1.88 (95% CI, 1.01–3.48), p = 0.045], or on Medicare [n = 122; HR 2.78 (95%CI, 1.76–4.38), p < 0.001], had inferior survival compared to patients with private insurance (n = 977; reference). In patients ≥65 years, no insurance-based survival differences were found (p = 0.10). Overall, significant insurance-based outcome disparities exist in WM. Further work is desperately needed to systematically uncover and address these disparities. [ABSTRACT FROM AUTHOR]

Objective. To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Methods. Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. Results. There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5–2.2], p < 0.001), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28–6.82], p < 0.001). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86–10.90], p < 0.001. Conclusions. There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH. [ABSTRACT FROM AUTHOR]

Summary: Belantamab mafodotin (BLMF) is a B‐cell maturation antigen‐directed antibody‐drug conjugate, recently approved for advanced multiple myeloma (MM). The impact of BLMF‐induced ocular toxicity on patient outcomes is unknown. We studied a cohort of 38 consecutively seen patients treated with BLMF outside of trials. Of those, 75% experienced ocular toxicity, with 69% developing keratopathy. Among patients requiring ocular toxicity‐related permanent BLMF discontinuation (14%) or dose reduction (11%), 70% had progression of MM within a median of 3 months (95% confidence interval: 0.2–not reached) following BLMF interruption or dose reduction. Ocular toxicity is a major deterrent to the continuous use of BLMF in routine clinical practice. Measures to successfully prevent and mitigate ocular toxicity should be developed to achieve the full potential of this agent. [ABSTRACT FROM AUTHOR]

There is increasing evidence that social infrastructure and a healthy social network can improve cancer survival. Mayo Clinic has an outpatient stem cell transplantation program for myeloma. Safe outpatient transplantation requires a caregiver to be present. Patients lacking a caregiver are transplanted as an inpatient. We reviewed outcomes on over 2000 patients with multiple myeloma, 2103 transplanted as an outpatient compared with 41 hospitalized for transplantation. Although progression-free survival following transplantation was identical between the two groups, overall survival was shorter in those hospitalized. This suggests that the absence of a caregiver for transplantation is an important surrogate of the social infrastructure associated with poor outcomes in transplanted patients with multiple myeloma [ABSTRACT FROM AUTHOR]

This is a retrospective study of patients with multiple myeloma (MM) who were >75 years old. We identified 394 patients and for non-trial patients (n = 350), immunomodulatory drug (IMiD)+dex (32%) was the most commonly used regimen followed by alkylator with steroids or other therapy (21%), alkylator + proteasome inhibitor (PI)+steroid (18%), and IMiD + PI + dex (13%). Overall, achieving ≥ very good partial response was more in patients receiving a triplet compared to other therapies (46% vs. 21%, p < 0.0001). Also, the median overall survival (OS) was significantly longer in patients who were treated with a triplet (median OS: 50.2 vs. 32.8 months, p = 0.0006). In a multivariate for OS, receiving a triplet (HR: 0.65, p = 0.02), not having an R-ISS stage 3 (HR: 0.36, p = 0.0003), and bone marrow plasma cell percentage <60% (HR: 0.69, p = 0.03) were predictive. In conclusion, being able to receive triplet therapy was associated with better survival in our MM patients >75 years old. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current study was conducted to determine characteristics distinguishing the 10-year survivor group in patients with systemic immunoglobulin light chain (AL) amyloidosis who underwent autologous stem cell transplantation (SCT). METHODS: The study group included all 74 patients with AL amyloidosis who underwent high-dose melphalan treatment supported by autologous SCT since the beginning of the Mayo Clinic's SCT program until prior to August 2001. RESULTS: A total of 32 patients (43%) patients survived for > 10 years. Statistically significant baseline differences in the 10-year survivor group included: 1) the number of organs involved; 2) septal thickness; 3) total cholesterol; and 4) urine total protein. The number of organs involved was the only predictor found on multivariable analysis. Depth of the response to therapy, as measured by the lowest posttransplantation serum free light chain level, was found to be the most significant indicator of durability of response. CONCLUSIONS: Autologous SCT can offer durable benefit for patients with AL amyloidosis. The number of organs involved offers the greatest pretreatment prognostic value, whereas the lowest posttransplantation serum free light chain level offers the best posttreatment prognostic value. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article describes two case studies of a 70-year-old female patient with a 14-year history of multiple myeloma and a 64-year-old male patient with a six-year history of multiple myeloma. The female patient was treated with pomalidomide 2 milligrams daily plus dexamethasone 40 milligrams weekly. The male patient received steroid treatment for 50 days.

OBJECTIVE: To examine whether the outcome of patients with primary systemic amyioidosis (AL) has improved over time and to identify predictors of early mortality in patients with AL. PATIENTS AND METHODS: We studied 2 separate cohorts of patients. The first cohort, consisting of 1998 patients with AL seen at Mayo Clinic between January 1977 and August 2006, was used to examine the trends in overall survival (OS) from diagnosis during this 30-year period. The second cohort, consisting of 313 patients seen between September 2006 and August 2009, was used to validate a model for predicting early mortality. RESULTS: The 4-year OS from diagnosis improved during each decade of follow-up: 21%, 24%, and 33%, respectively, for the periods 1977-1986,1987-1996, and 1997-2006 (P<.001). Within the last group (1997.2006), 4-year OS during 1997-1999,2000-2002, and 2003-2006 was 28%, 30%, and 42%, respectively (P=.02). However, the 1-year mortality remained high during the 30-year period. A risk stratification score using cardiac troponin T, N-terminal pro-brain natriuretic peptide, and uric acid identified patients at risk of early mortality. The 1-year mortality with 0, 1, 2, or 3 risk factors was 19%, 37%, 61%, and 80%, respectively, in this training cohort of 459 patients. This was confirmed in a validation cohort of 313 patients. CONCLUSION: Survival in AL has improved over time, with maximum improvement occurring in the past decade. However, early mortality remains high, and prospective identification of patients at risk of early mortality may allow development of risk-adapted strategies. [ABSTRACT FROM AUTHOR]

Dexamethasone (Dex), alone or in combination, is commonly used for treating multiple myeloma. Dex as single agent for initial therapy of myeloma results in overall response rates of 50–60%. It is unclear whether steroid responsiveness reflects any biological characteristic that impacts long-term outcome. We studied a cohort of 182 patients with newly diagnosed myeloma seen between March 1998 and June 2007, initially treated with single-agent Dex for at least 4 weeks. The median age at diagnosis was 63 years (range, 39–81) and the median estimated survival was 55 months. At a median duration of therapy of 15 weeks, 91 (50%) patients had a partial response or better, 80 (44%) had less than partial response and the remaining (6%) patients were not evaluable. The median overall survival from diagnosis for the responders was 75 months compared to 71 months for remaining patients, P = 0·6.There was no correlation between baseline disease characteristics and Dex responsiveness. While overall survival was longer for the 130 (70%) patients who proceeded to an autologous stem cell transplant, no correlation was found between survival and Dex responsiveness among either group. Among this cohort of patients with myeloma, failure to respond to single agent steroid did not have an adverse impact on eventual outcome. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify and assess the clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma (MM). PATIENTS AND METHODS: From a prospectively maintained database, we identified 47 patients seen between January 1, 1990, and August 31, 2008, with a diagnosis of AL amyloidosis that was made at least 6 months after MM diagnosis; these patients form the study group. RESULTS: Among the 47 patients, 36 developed typical features, 3 had atypical features, and 8 had an incidental finding of amyloidosls. Amyloid deposits were demonstrated in bone marrow, subcutaneous fat aspirate, or organ biopsy in 24, 19, and 12 patients, respectively. One organ was involved in 29 patients (62%), whereas 11 patients (23%) had involvement in more than one organ. At diagnosis of AL amyloidosis, treatment was changed or started in 22 patients, whereas the same treatment was continued In 21 patients, and no treatment data were available for the rest. The best hematologic response included partial response or better in 11 patients (23%) and stable disease in 18 patients (38%). Improvement in an organ was seen in 3 of the 21 evaluable patients. The median overall survival from diagnosis of AL amyloidosis was 9.1 months (95% confidence interval, 4-14). Of the 6 patients still alive, 2 underwent peripheral blood stem cell transplant, and none had cardiac involvement or involvement in more than one organ. CONCLUSION: Delayed onset of AL amyloidosis is rarely seen In patients with MM and requires a high index of suspicion for prompt diagnosis. Outcome of these patients is poor, especially In the presence of cardiac involvement. [ABSTRACT FROM AUTHOR]

Background. The kidney is affected by immunoglobulin light chain amyloidosis (AL) in more than 50% of patients who present with the disease, but long-term predictors for and outcomes after renal replacement therapy are not well described. [ABSTRACT FROM PUBLISHER]

A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27·5 months vs. 17·2 months, P = 0·01), and longer overall survival (OS) from transplant (80·2 months vs. 48·3 months, P = 0·03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post-transplant relapse independent of other known risk factors. Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the prognostic value of serum uric acid (UA) in patients with primary systemic (light chain) amyloidosis (AL). PATIENTS AND METHODS: A cohort of 1977 patients with newly diagnosed AL seen at our institution between April 1, 1960, and August 1, 2006, and 293 patients with AL who underwent peripheral blood stem cell transplant between March 1, 1996, and October 1, 2006, were studied retrospectively to examine the value of serum UA. The prognostic value of several variables was examined using Cox proportional hazards models, and the survival time was estimated using Kaplan-Meier analysis; curves were compared using the log-rank test. RESULTS: Patients with UA levels greater than 8 mg/dL had a median overall survival of 9 months from diagnosis compared with 20.3 months for the remaining patients (P<.001). The prognostic value of UA was independent of the known cardiac prognostic markers cardiac troponin T (cTnT) and N-terminal propeptide of brain-type natriuretic peptide (NTProBNP). Addition of UA to these factors allows us to classify patients into 4 groups with significantly different outcomes. Patients with none, 1, 2, or 3 of these risk factors (UA, >8 mg/dL; cTnT, >0.035 ng/mL; and NTProBNP, >332 pg/mL) had a median overall survival of 36.6, 29.2, 11.1, and 3.6 months, respectively (P<.001). Similarly, UA levels helped predict overall survival in patients undergoing peripheral blood stem cell transplant for AL and added to the value of cTnT and NTProBNP. CONCLUSION: The data confirm the prognostic utility of cTnT and NTProBNP in a large group of patients and highlight the value of serum UA in allowing better forecasting of probable outcomes for patients with AL. [ABSTRACT FROM AUTHOR]

Bisphosphonate chemotherapy is commonly used In the treatment of bone diseases such as osteoporosis, Paget disease, and multiple myeloma and to limit bone pain and hypercalcemia associated with malignant metastatic bone lesions. The introduction of bisphosphonate therapy has Improved the quality of life In a vast majority of patients, showing clear medical efficacy. However, since 2003 a growing number of reports have described necrotic bone lesions (osteonecrosis of the jaw [ONJ]) affecting maxillofacial bones in patients who have received chemotherapy with intravenous bisphosphonate therapy. Unfortunately, the development of ONJ has been refractory to conventional treatment modalities. Several treatment options have been proposed for ONJ, most of which focus primarily on conservative management with local irrigation and empirical long-term antibiotic therapy. However, results of treatment have been associated with high failure rates, progression of disease, and continued decline in patients' quality of life. We describe 2 patients in whom primary surgical salvage was performed successfully for ONJ. Our experience indicates that with appropriate technique, primary surgical treatment may offer benefit to selected patients with ONJ. [ABSTRACT FROM AUTHOR]

High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is an accepted form of treatment for patients with AL amyloidosis. The purpose of the current study is to review the outcomes of IgM AL amyloidosis patients treated with high dose chemotherapy and autologous stem cell transplant and compare them to the outcomes of all AL amyloidosis subtypes treated similarly. We retrospectively reviewed the pretransplant characteristics, conditioning regimens and response to transplant of all twelve IgM AL amyloidosis patients who were transplanted at the Mayo Clinic between May 1999 and August 2005. Transplant related mortality was low at 8%. The overall hematologic response rate was 89%. The organ response rate was 67%. Overall median survival has not been reached as eleven patients are still alive. IgM AL amyloidosis patients appear to have similar outcomes after HDC and ASCT as other subtypes of AL amyloidosis suggesting that this therapy is an acceptable form of treatment for patients with IgM amyloidosis, and should be considered as a first line treatment option. [ABSTRACT FROM AUTHOR]

Although imatinib was designed to specifically inhibit the bcr-abl gene product, it inhibits other receptor tyrosine kinases including c-kit. As pre-clinical data, 126 patients with plasma cell disorders and 19 controls were evaluated for c-kit expression. Patients were eligible for the treatment trial if they had relapsed/refractory myeloma. The primary end-point of the study was response. Of the 145 studied before the trial, c-kit expression was present on the bone marrow plasma cells of control (11%), AL amyloid (53%), MGUS (47%), SMM (67%) and MM (42%) patients. Twenty-three MM patients were enrolled on the therapeutic trial (imatinib 400 mg daily) and 52% had positive c-kit staining. There were no responses. The median duration of treatment was 48 days (range: 12–349). Patients ended treatment due to progressive disease (18 patients), death (3) and other (2). The data suggest that imantinib is not an active agent in patients with relapsed or refractory multiple myeloma. [ABSTRACT FROM AUTHOR]

Background. High-dose chemotherapy and stem cell transplantation are being applied increasingly to the treatment of selected patients with multiple myeloma or primary systemic amyloidosis. Stem cell transplantation presents unique challenges to the nephrologist because of the high prevalence of renal involvement in myeloma and the issues that are associated with high-dose chemotherapy in patients with the nephrotic syndrome due to renal amyloid. Methods. We review the published literature on stem cell transplantation in patients with reduced renal function. Results and Conclusions. The specifics of transplantation pertaining to patients with renal amyloid nephrotic syndrome are discussed in detail. [ABSTRACT FROM AUTHOR]

Summary: Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow‐up of 9·5 [8·1–11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and β2‐microglobulin (β2M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time‐to‐progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7–8·7) vs. 4·7 (2·4–7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C‐X‐C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT, P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age‐, sex‐ and calendar year‐matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and β2M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre‐emptive intervention in this patient population. [ABSTRACT FROM AUTHOR]

Notably, however, IFE did not detect BM in the same IgG lambda MM patient with hypogammaglobulinemia spiked at I C i SB max sb , or in any of the three patients receiving BM. (E) IFE of BM spiked at Cmax of 42 mcg/mL in the same IgG lambda MM patient from panel C. (F-H) IFE of 3 myeloma patients on BM therapy (Table 1, patients 2, 3, and 4, respectively). Keywords: belantamab mafodotin; immunofixation; mass spectrometry; multiple myeloma EN belantamab mafodotin immunofixation mass spectrometry multiple myeloma e430 e433 4 10/18/21 20210915 NES 210915 To the Editor, Monoclonal antibodies (mAbs) such as daratumumab and elotuzumab have emerged as novel, effective therapies for relapsed/refractory multiple myeloma (MM). [Extracted from the article]

Summary: Measurable residual disease (MRD) assessment by marrow‐based next‐generation flow cytometry (NGF) following autologous stem cell transplantation (ASCT) may lead to false‐negative results due to patchy marrow involvement and extramedullary disease in patients with multiple myeloma. We assessed the value of simultaneous MRD evaluation with NGF and serum matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MASS‐FIX). Of all 61 complete responders who were NGF‐negative for MRD, around day‐100 post ASCT, 59% were MASS‐FIX‐positive. At median follow‐up of 26 months, 69% of MASS‐FIX(+)/NGF(−) patients were alive and progression‐free versus 96% of MASS‐FIX(‐)/NGF(−) patients, P = 0·02. MASS‐FIX, a simple peripheral blood‐based assay complements marrow‐based NGF to accurately prognosticate patients with myeloma. [ABSTRACT FROM AUTHOR]

Introduction: Little is known on continued response following completion of therapy in light chain (AL) amyloidosis. Methods: We studied 373 AL amyloidosis patients who achieved complete response (CR) or very good partial response (VGPR) to first‐line therapy. Results: By end of therapy (EOT), 46% of patients achieved a CR and 54% a VGPR. With no further therapy, 17.5% of patients were upstaged from VGPR to CR (delayed CR), with a median of 9 months. Compared with CR and VGPR at EOT, patients with a delayed CR were characterized by higher proportion of t(11;14) and lower rate of trisomies. Autologous stem cell transplant was more frequent in the delayed CR group. Patients with a delayed CR were characterized by minimal residual disease negativity and organ response rates similar to patients with CR at EOT and higher than patients achieving VGPR at EOT. Patients with a delayed CR had a longer PFS/OS compared to patients with CR or VGPR by EOT (median PFS 149 vs 92 vs 52 months, P <.001; 10‐year OS 87% vs 71% vs 56%, P <.001). Conclusions: This study characterizes delayed CR in AL amyloidosis, highlights its prognostic impact which is at least similar to those who achieved CR at EOT, and underlines another aspect of response monitoring. [ABSTRACT FROM AUTHOR]

Waldenstrom macroglobulinemia (WM) has an annual incidence of 3–3.2 cases per million-person/year. National Cancer Data Base was used to identify newly diagnosed WM cases requiring initiation of therapy and their annual facility volume was used to divide the treatment facilities into four quartiles (Qs). Cox regression was used to analyze the association between facility volume and survival, adjusted by demographics, socioeconomic, geographic, comorbidity factors and year of diagnosis. A total of 3064 patients treated in 795 facilities were included. The unadjusted median overall survival (OS) by facility volume was: Q1:6.5 years (5-year OS 55%), Q2:7 years (5-year OS 60%), Q3:8 years (5-year OS 64%), and Q4: NR (5-year OS 71%), p < 0.0001. Our results demonstrated that a volume–outcome relationship exists in WM and is an independent predictor of overall survival in addition to the established risk factors as age and disease severity. [ABSTRACT FROM AUTHOR]

Waldenström Macroglobulinemia (WM) is a rare, indolent B-cell lymphoma characterized by lymphoplasmacytic involvement of the bone marrow and serum IgM monoclonal protein of any size [[1]]. Of 893 consecutively seen WM patients, with a median follow-up of 9 years (95% CI, 8.4-9.7), 387 patients were placed into either the short-term survival group ( I n i = 171, 19%) or the long survival group ( I n i = 216, 24%). The median OS for the long survival group was not reached (IQR = 13.5 years-not reached) and the median age at diagnosis was 62 years (31-85 years); 50 (76%) patients died from causes related to WM and 16 (24%) from causes unrelated to WM. Another study from our institution reported that 10-year OS was 66% for patients with I MYD88 SP WT sp i and 61% for patients with I MYD88 i SP L265P sp ( I p i = 0.52), despite patients with I MYD88 i SP WT sp having a shorter time-to-transformation (5-year rate of 16% for I MYD88 i SP WT sp vs. 2.8% for the I MYD88 i SP L265P sp ) [[19]]. [Extracted from the article]