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Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint.

In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6–12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.

CARTITUDE-2 (NCT04133636), a phase 2, multicohort study evaluating safety and efficacy of the anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapy ciltacabtagene autoleucel (cilta-cel) in patients (pts) with multiple myeloma (MM). We present updated efficacy and safety data from CARTITUDE-2 cohorts A and B with a median follow-up (MFU) of ∼29 mo.

Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT).

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N= 248; ECOG performance status of 0–1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1–20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2–36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9–5.6) and 12.4 months (95% CI: 10.3–NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n= 74), TEAEs (n= 19), and other reasons (n= 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action.

ABSTRACTWith the introduction of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, major improvements have been achieved in the treatment of multiple myeloma (MM), with a significant impact on the outcome of this disease. Different treatment combinations are now in use and other therapies are being developed. Based on an extensive review of the recent literature, we propose practical recommendations on myeloma management, to be used by hematologists as a reference for daily practice.

Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (−8.9) and disease symptoms (−10.2), and by month 2 for fatigue (−7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748.

Bei der Impfung handelt es sich um eine der erfolgreichsten medizinischen Maßnahmen, die bereits Millionen von Menschen das Leben gerettet hat. Die Impfung ist besonders wichtig bei Patienten mit einem Multiplen Myelom, deren Infektionsrisiko aufgrund der krankheitsinhärenten Immunsuppression sowie der immunsuppressiven Wirkung der Therapie erhöht ist. Daher sollten alle geeigneten Maßnahmen ergriffen werden, um eine wirksame Immunantwort gegen weitverbreitete Krankheitserreger wie Influenza, Pneumokokken, das Varicella-Zoster-Virus sowie gegen Bakterien und Viren (Haemophilus influenzae, Meningokokken und Hepatitis), die häufig ein erhebliches Risiko für Patienten mit einem Multiplen Myelom darstellen, anzuregen. Patienten nach autologer und insbesondere nach allogener Transplantation haben stark reduzierte Antikörpertiter und benötigen daher ein breiteres Impfspektrum. Die Impfreaktion ist bei Myelom-Patienten oft weniger stark ausgeprägt als in der Allgemeinbevölkerung, sodass entweder die Messung der Antikörpertiter nach der Impfung und/oder eine Wiederholungsimpfung erforderlich ist. In dieser Arbeit stellen wir die Daten zusammen, die zur Impfung von Patienten mit Multiplem Myelom existieren, und geben Empfehlungen für die klinische Praxis.

Patients with multiple myeloma frequently present with substantial immune impairment and an increased risk for infections and infection-related mortality. The risk for infection with SARS-CoV-2 virus and resulting mortality is also increased, emphasising the importance of protecting patients by vaccination. Available data in patients with multiple myeloma suggest a suboptimal anti-SARS-CoV-2 immune response, meaning a proportion of patients are unprotected. Factors associated with poor response are uncontrolled disease, immunosuppression, concomitant therapy, more lines of therapy, and CD38 antibody-directed and B-cell maturation antigen-directed therapy. These facts suggest that monitoring the immune response to vaccination in patients with multiple myeloma might provide guidance for clinical management, such as administration of additional doses of the same or another vaccine, or even temporary treatment discontinuation, if possible. In those who do not exhibit a good response, prophylactic treatment with neutralising monoclonal antibody cocktails might be considered. In patients deficient of a SARS-CoV-2 immune response, adherence to measures for infection risk reduction is particularly recommended. This consensus was generated by members of the European Multiple Myeloma Network and some external experts. The panel members convened in virtual meetings and conducted an extensive literature research and evaluated recently published data and work presented at meetings, as well as findings from their own studies. The outcome of the discussions on establishing consensus recommendations for COVID-19 vaccination in patients with multiple myeloma was condensed into this Review.

To understand the profile of best responders (complete response or better [≥CR]) to carfilzomib, we described the characteristics, progression-free survival (PFS), overall survival (OS) data, and the safety of patients who achieved ≥CR to carfilzomib-based treatment in ASPIRE and ENDEAVOR. In post hoc analyses from ASPIRE and ENDEAVOR, median PFS and OS were longer for ≥CR patients versus those who achieved a very good partial response or partial response (VGPR/PR). In the carfilzomib arm of ASPIRE, median PFS was 50.4 months for ≥CR versus 22.1 months for VGPR/PR; median OS was 67.0 versus 44.2 months, respectively. In the carfilzomib arm of ENDEAVOR, median PFS was 34.0 for ≥CR versus 20.4 months for VGPR/PR; median OS was non-estimable. Despite the longer treatment duration, fewer patients with ≥CR versus VGPR/PR experienced treatment-emergent adverse events that led to discontinuation of carfilzomib-based treatment in ASPIRE or ENDEAVOR. Low serum lactate dehydrogenase was the only factor associated with achieving ≥CR vs patients not achieving CR in ASPIRE in multivariate regression analyses. No association was found between cytogenetic risk status and reaching ≥CR. Carfilzomib treatment may lead to rapid and deep responses, irrespective of most patient characteristics.

Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections due to the disease-inherent immune suppression, and because of the immune suppressive effects of therapy. Hence, all appropriate measures should be exploited, to elicit an effective immune response to common pathogens like influenza, pneumococci, varicella zoster virus, and to those bacteria and viruses (haemophilus influenzae, meningococci, and hepatitis) that frequently may pose a significant risk to patients with multiple myeloma. Patients after autologous, and specifically after allogeneic transplantation have severely reduced antibody titers, and therefore require a broader spectrum of vaccinations. Response to vaccination in myeloma often is less vigorous than in the general population, mandating either measurement of the postvaccination antibody titers and/or repeating the vaccination. Here, we compile the existing data on vaccination in multiple myeloma and provide recommendations for clinical practice.

We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n?=?446), auto-auto (n?=?105), or auto-allo (n?=?72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45–58%) for single auto, 60% (95% CI, 49–72%) for auto-auto, and 67% (95% CI, 53–80%) for auto-allo (p?=?0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12–22%), 33% (95% CI, 22–43%), and 34% (95% CI, 21–38%; p?=?0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p?=?0.007) and auto-allo (HR, 0.45; p?=?0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p?=?0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p?=?0.097). No significant difference in OS was identified between the groups in patients with del(17p).

ABSTRACTObjective: The aim of this study was to evaluate the administration of intravenous immunoglobulin (IVIg) solutions (5% vs. 10%) in hematological patients suffering from a secondary immunodeficiency (SID) to optimize infusion duration and hospitalization time.Design: A monocentric, observational study in 30 patients with secondary hypogammaglobulinemia due to a lymphoproliferative disorder currently under IVIg 5% treatment. A sequential approach was followed with observations during IVIg 5% and 10% administration 3 to 4 weeks later. Infusion time, time spent at the day clinic, IVIg-related adverse events and number of actions taken by the nursing staff were evaluated and compared between the 5% and 10% infusions. Questionnaires for patients and nursing staff were obtained after IVIg 10% to assess their satisfaction with the change of infusion.Results: Average infusion time was reduced from 4.92 h to 2.29 h (p < 0.0001). Time spent at the day clinic was 5.87 h for the 5% IVIg administration and 4.56 h for the 10% (p = 0.0005). IVIg-related adverse events rose from 0 to 0.43 per patient. No serious adverse events were reported. Nursing actions per patient decreased from 1.03 to 0.67. Patient and nursing satisfaction were respectively 83% and 96% in favor of IVIg 10%.Conclusion: A 10% IVIg solution can significantly reduce infusion time and overall duration of the day clinic visit. Care must be taken to minimize new infusion-related adverse events. Switching to a 10% IVIg administration increases patient and nursing satisfaction but also requires additional workflow changes to further shorten the day clinic visit.

Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma.

Introduction

Introduction:CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel), an anti-BCMA chimeric antigen receptor (CAR)-T cell therapy, in various populations of patients with multiple myeloma (MM). We previously reported 17-month median follow-up results from cohort A (1-3 prior lines of therapy [LOT] and lenalidomide [len]-refractory) and 18-month median follow-up results from cohort B (early relapse: ≤12 months after either autologous stem cell transplant [ASCT] or start of initial anti-myeloma treatment, if not transplanted). Cilta-cel is also under evaluation in patients with len-refractory MM after 1-3 LOT in the phase 3 CARTITUDE-4 study, which showed cilta-cel significantly prolonged progression-free survival (PFS) vs standard of care (HR, 0.26) at a median follow-up of 16 months. Here, we present updated efficacy and safety data from CARTITUDE-2 cohorts A and B, both with a median follow-up of ~29 months.

Introduction:DARA plus bortezomib, thalidomide, and dexamethasone (D-VTd) quadruplet therapy has shown clinical benefit versus VTd alone and is approved for transplant-eligible pts with NDMM. VRd induction followed by autologous stem cell transplant (ASCT), VRd consolidation, and lenalidomide (R) maintenance is also considered a standard of care for transplant-eligible NDMM. In the phase 2 GRIFFIN study, intravenous DARA combined with VRd (D-VRd) induction/consolidation followed by D-R maintenance improved depth of response and progression-free survival (PFS) versus VRd induction/consolidation and R maintenance in transplant-eligible pts with NDMM after >4 years of follow-up. The phase 3 PERSEUS study is evaluating subcutaneous DARA (DARA SC) in combination with VRd induction/consolidation followed by D-R maintenance versus VRd induction/consolidation and R maintenance in transplant-eligible NDMM. Here we report the primary analysis of PERSEUS.

Introduction:Patients with TCE RRMM have a high disease burden and often report worsening HRQoL with additional lines of therapy. The single-arm, phase 2 KarMMa study demonstrated that ide-cel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy, improved HRQoL from baseline in patients with TCE RRMM who had received ≥ 3 prior regimens (Delforge M, et al. Blood Adv2022;6:1309-1318). Furthermore, in the phase 3 KarMMa-3 clinical trial (NCT03651128), ide-cel significantly improved progression-free survival and response compared with standard regimens in patients with TCE RRMM who had received 2-4 prior regimens (Rodriguez-Otero P, et al. N Engl J Med2023;388:1002-1014).

Introduction:Patients (pts) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) represent a particularly difficult-to-treat population. A pooled analysis of the prospective, non-interventional, multinational LocoMMotion (NCT04035226) and MoMMent (NCT05160584) studies previously demonstrated suboptimal outcomes in pts with TCE RRMM. Extramedullary disease (EMD) is an aggressive feature of multiple myeloma characterized by the presence of plasmacytomas that have spread beyond the bone marrow. A recent systematic literature review (Bladé et al, 2022) found that the prognosis of pts with EMD is poor, as most current treatment (tx) options are notably less efficacious in pts with EMD than in those without EMD. The review also found that there are few prospective studies evaluating tx approaches in pts with EMD. Additional prospective data are needed to better understand current txs and outcomes for pts with EMD. In this analysis, we describe current txs and outcomes in pts with TCE RRMM with EMD over the past 3 years in LocoMMotion and MoMMent.

Background:An interim analysis (data cutoff date April 18, 2022) of the international, open-label, phase 3 KarMMa-3 trial (NCT03651128) showed the chimeric antigen receptor T cell therapy idecabtagene vicleucel (ide-cel) significantly improved progression-free survival and treatment response rates, as well as HRQoL, as compared with standard regimens, in patients with triple-class exposed (TCE) RRMM who had received 2-4 prior regimens (Rodriguez-Otero P, et al. N Engl J Med2023;388:1002-1014; Delforge M, et al., HemaSphere, 2023;7(S3):P905). The aim of the present study was to analyze the effect of ide-cel versus standard regimens (daratumumab [DARA], pomalidomide, and dexamethasone [DEX]; DARA, bortezomib, and DEX; ixazomib, lenalidomide, and DEX; carfilzomib and DEX; or elotuzumab, pomalidomide, and DEX) on HRQoL in KarMMa-3 trial participants with an extended follow-up of patient-reported outcomes (PRO) data collection (data cutoff date April 28, 2023).

Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma. We evaluated whether the addition of daratumumab to VTd before and after autologous stem-cell transplantation would improve stringent complete response rate in patients with newly diagnosed multiple myeloma.

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months’ follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39.

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P< .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P= .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.govas #NCT00689936 and EudraCT as 2007-004823-39.

The treatment of multiple myeloma is considered a continuously evolving paradigm as a result of the growing availability of new and highly effective drugs, including first- and second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. Clinical trials advocate long-term rather than short-term treatment schedules with combinations of these new anti–myeloma drug classes. Although the overall toxicity profile of the recommended regimens can be considered favorable, their increasing complexity and prolonged use warrant a heightened vigilance for early and late side effects, a priori because real-life patients can be more frail or present with 1 or more comorbidities. The treatment decision process, at diagnosis and at relapse, therefore requires myeloma physicians to carefully balance efficacy and toxicity profiles for each individual patient. Early and/or unnecessary tapering or treatment discontinuation for drug-related adverse events may not only reduce patients’ quality of life, but also negatively impact their outcome. Accurate knowledge in recognizing and managing the potential side effects of present-day treatment regimens is therefore a cornerstone in myeloma care. Using 5 case vignettes, we discuss how to prevent and manage the most common nonhematological adverse events of anti–myeloma treatment regimens containing proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies.

The treatment of multiple myeloma is considered a continuously evolving paradigm as a result of the growing availability of new and highly effective drugs, including first- and second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. Clinical trials advocate long-term rather than short-term treatment schedules with combinations of these new anti–myeloma drug classes. Although the overall toxicity profile of the recommended regimens can be considered favorable, their increasing complexity and prolonged use warrant a heightened vigilance for early and late side effects, a priori because real-life patients can be more frail or present with 1 or more comorbidities. The treatment decision process, at diagnosis and at relapse, therefore requires myeloma physicians to carefully balance efficacy and toxicity profiles for each individual patient. Early and/or unnecessary tapering or treatment discontinuation for drug-related adverse events may not only reduce patients' quality of life, but also negatively impact their outcome. Accurate knowledge in recognizing and managing the potential side effects of present-day treatment regimens is therefore a cornerstone in myeloma care. Using 5 case vignettes, we discuss how to prevent and manage the most common nonhematological adverse events of anti–myeloma treatment regimens containing proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies.

Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.gov identifier NCT01712789.

Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.govidentifier NCT01712789.

Hodgkin's lymphoma is one of the most common lymphoid neoplasms in young adults, but the low abundance of neoplastic Hodgkin/Reed-Sternberg cells in the tumour hampers the elucidation of its pathogenesis, biology, and diversity. After an incidental observation that genomic aberrations known to occur in Hodgkin's lymphoma were detectable in circulating cell-free DNA, this study was undertaken to investigate whether circulating cell-free DNA can be informative about genomic imbalances in Hodgkin's lymphoma.

SUMMARY Aim: We conducted a retrospective single center study to measure bone healing by conventional x-ray radiographs (CXR) and computer tomography (CT) in multiple myeloma patients treated with bortezomib. Imaging data were correlated with serum levels of alkaline phosphatases and with disease response. Materials & methods: We identified 26 multiple myeloma patients receiving six or more 3-weekly cycles of bortezomib with radiological assessments. Imaging data before, during and after bortezomib, were analyzed for signs of bone healing. Results: In the group of CXR, 8/21 patients (38) had evidence of bone healing compared with 7/10 patients (70) in the CT group. Signs of bone healing were observed after an average of 28 (CXR) or 30 (CT) bortezomib administrations. Alkaline phosphatases did not correlate with bone healing or with disease response. Conclusion: In 13/26 (or 50) of patients a beneficial bortezomib-related skeletal effect could be detected. This retrospective study provides further evidence for skeletal improvement during treatment with bortezomib.

Delforge: Amgen, Celgene, Janssen, Takeda: Honoraria. Baz:Sanofi, Karypharm, Janssen, Celgene: Other: Advisory board; Karyopharm, janssen, Bristol Myers Squibb, Celgene, Merck, Sanofi, Abbvie Inc.: Research Funding. Cavo:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Callander:University of Wisconsin: Current Employment; Cellectar: Research Funding. Ghobadi:Atara: Consultancy; Celegene: Consultancy; EUSA: Consultancy; Wugen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau. Rodriguez-Otero:GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company, Honoraria; Kite: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Sanofi: Consultancy, Honoraria; Medscape: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Mateos:Adaptive Biotechnologies: Honoraria; GlaxoSmithKline: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; EDO Mundipharma: Honoraria; Seattle Genetics: Honoraria; Roche: Honoraria. Massaro:bluebird bio: Current Employment, Current equity holder in publicly-traded company. Ding:Bristol-Myers Squibb Company: Current Employment. Patel:BMS: Current Employment. Pittari:Bristol-Myers Squibb Company: Current Employment. Novick:Bristol-Myers Squibb Company: Current Employment. Giralt:OMEROS: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria, Research Funding; KITE: Consultancy; MILTENYI: Consultancy, Research Funding; ACTINUUM: Consultancy, Research Funding; TAKEDA: Research Funding; AMGEN: Consultancy, Research Funding; JAZZ: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Research Funding. Berdeja:Bioclinica: Consultancy; CURIS: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Constellation: Research Funding; Abbvie: Research Funding; Glenmark: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; EMD Sorono: Research Funding; Kesios: Research Funding; Kite Pharma: Consultancy; Legend: Consultancy; Lilly: Research Funding; Novartis: Research Funding; Poseida: Research Funding; Prothena: Consultancy; Teva: Research Funding; Bluebird: Research Funding; BMS: Consultancy, Research Funding; Cellularity: Research Funding; Genentech, Inc.: Research Funding; Servier: Consultancy; Amgen: Consultancy, Research Funding; Acetylon: Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy.

Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Delforge:Amgen: Honoraria; BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bertin:ICON plc: Current Employment. Tahir:ICON plc: Current Employment. Lewis:ICON plc: Current Employment. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Campbell:BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda:BMS: Current Employment, Current equity holder in publicly-traded company. Munshi:Takeda: Consultancy; C4: Current equity holder in private company; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy.

Patients with relapsed and refractory multiple myeloma (RRMM) who progress on immunomodulatory agents, proteasome inhibitors (PIs), and anti-CD38 antibodies have poor outcomes, highlighting the need for novel targets for the disease. The BCMA-directed CAR T cell therapy ide-cel previously demonstrated deep, durable responses in heavily pretreated patients with RRMM (Raje N, et al. N Engl J Med.2019;380:1726-1737; Munshi NC, et al. J Clin Oncol.2020;38[suppl] [abstract 8503]). In the pivotal phase 2 KarMMa study, overall response rate (ORR), complete response rate, and median duration of response (DOR) were 73%, 33%, and 10.7 months, respectively, across the target dose levels of 150−450 × 106CAR+ T cells, and 82%, 39%, and 11.3 months at the highest target dose of 450 × 106CAR+ T cells. In order to examine the effect of ide-cel as an earlier line of treatment, the multicenter, randomized, open-label, phase 3 study, KarMMa-3, was opened to compare ide-cel vs standard regimens in patients whose disease is refractory to the last line of therapy.

Introduction: Idecabtagene vicleucel (ide-cel, bb2121) is a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy under investigation in the KarMMa trial as a treatment for patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies. In the phase 2 KarMMa trial, ide-cel demonstrated a favorable benefit-risk profile in this patient population (Munshi NC, et al. J Clin Oncol2020;38:8503). Ide-cel also demonstrated clinically meaningful improvements in the key health-related quality of life (HRQoL) symptoms associated with MM (Delforge M, et al. HemaSphere2020;4:EP1000). Translating HRQoL data to health state utility values (HSUVs)/HRQoL weights is key to understanding the HRQoL impact of a treatment in relation to that of a healthy general population and is an important consideration in clinical decision making and health technology assessments. HSUVs are scored between 0 and 1, where 0 is death and 1 is perfect health. In the general population, individuals of a similar age range to patients with MM have HSUV scores of 0.83 in the USA, 0.80 in the UK, and 0.84 in Canada (Guertin JR, et al. CMAJ2018;190:E155-161; Janssen MF, et al. Eur J Health Econ2019;20:205-216). This analysis aimed to determine HSUVs for patients treated in the KarMMa study according to their progression status.

Although it is well established that BMP4 plays an important role in the development of hematopoietic system, it is less well understood whether BMP4 affects adult hematopoiesis and how. Here, we describe a novel mechanism by which BMP4 regulates homing of murine as well as human hematopoietic stem/progenitor cells (HSPCs). BMP4 treatment of murine BM derived c-kit+Lin−Sca-1+(KLS) and CD150+CD48−KLS cells for up to 5 days in vitro prevented the culture-induced loss of Integrin-α4 (ITGA4) expression as well as homing. The effect on ITGA4 expression in response to BMP4 is mediated via SMAD-independent phosphorylation of p38 MAPK, which activates microphthalmia-associated transcription factor (MITF), known to induce ITGA4 expression. Elevated ITGA4 expression significantly enhanced HSPC attachment to bone marrow stromal cells, homing and long-term engraftment of the BMP4 treated cells compared with the cells cultured without BMP4. BMP4 also induced expression of ITGA4 on human BM derived Lin−CD34+cells in culture, which was associated with improved homingpotential. Thus, BMP4 prevents culture-induced loss of ITGA4 expression on HSPCs in a SMAD-independent manner, resulting in improved homing of cultured HSPCs and subsequent hematopoietic reconstitution.

Although it is well established that BMP4 plays an important role in the development of hematopoietic system, it is less well understood whether BMP4 affects adult hematopoiesis and how. Here, we describe a novel mechanism by which BMP4 regulates homing of murine as well as human hematopoietic stem/progenitor cells (HSPCs). BMP4 treatment of murine BM derived c-kit+Lin−Sca-1+ (KLS) and CD150+CD48−KLS cells for up to 5 days in vitro prevented the culture-induced loss of Integrin-α4 (ITGA4) expression as well as homing. The effect on ITGA4 expression in response to BMP4 is mediated via SMAD-independent phosphorylation of p38 MAPK, which activates microphthalmia-associated transcription factor (MITF), known to induce ITGA4 expression. Elevated ITGA4 expression significantly enhanced HSPC attachment to bone marrow stromal cells, homing and long-term engraftment of the BMP4 treated cells compared with the cells cultured without BMP4. BMP4 also induced expression of ITGA4 on human BM derived Lin−CD34+ cells in culture, which was associated with improved homingpotential. Thus, BMP4 prevents culture-induced loss of ITGA4 expression on HSPCs in a SMAD-independent manner, resulting in improved homing of cultured HSPCs and subsequent hematopoietic reconstitution.