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Summary: The treatment pattern and outcomes in patients with indolent B‐cell lymphoma treated during the coronavirus disease 2019 (COVID‐19) pandemic period compared to the prepandemic period are unclear. This was a retrospective population‐based study using administrative databases in Ontario, Canada (follow‐up to 31 March 2022). The primary outcome was treatment pattern; secondary outcomes were death, toxicities, healthcare utilization (emergency department [ED] visit, hospitalization) and SARS‐CoV‐2 outcomes. Adjusted hazard ratios (aHR) from Cox proportional hazards models were used to estimate associations. We identified 4143 patients (1079 pandemic, 3064 prepandemic), with a median age of 69 years. In both time periods, bendamustine (B) + rituximab (BR) was the most frequently prescribed regimen. During the pandemic, fewer patients received R maintenance or completed the full 2‐year course (aHR 0.81, 95% CI 0.71–0.92, p = 0.001). Patients treated during the pandemic had less healthcare utilization (ED visit aHR 0.77, 95% CI 0.68, 0.88, p < 0.0001; hospitalization aHR 0.81, 95% CI 0.70–0.94, p = 0.0067) and complications (infection aHR 0.69, 95% CI 0.57–0.82, p < 0.0001; febrile neutropenia aHR 0.66, 95% CI 0.47–0.94, p = 0.020), with no difference in death. Independent of vaccination, active rituximab use was associated with a higher risk of COVID‐19 complications. Despite similar front‐line regimen use, healthcare utilization and admissions for infection were less in the pandemic cohort. [ABSTRACT FROM AUTHOR]

We conducted an analysis of indirect costs alongside the LY.12 randomized trial in patients with relapsed or refractory (R/R) aggressive non-Hodgkin lymphoma (NHL). Lost productivity data for Canadian patients and caregivers in the trial were collected at baseline and with each chemotherapy cycle pre-transplant, using an adapted Lost Productivity questionnaire. Mean per patient indirect costs were CAD 2999 for patients in the GDP arm and CAD 3400 in the DHAP arm. A substantial majority was not working or had to reduce their workload during this treatment time. Salvage chemotherapy for R/R aggressive NHL is associated with significant indirect costs to patients and their caregivers. [ABSTRACT FROM AUTHOR]

High dose chemotherapy followed by autologous stem cell transplant (ASCT) is a cornerstone of frontline therapy for multiple myeloma (MM) [[1]]. Four of the ten transplants were performed as second-line therapy, including two for relapsed disease 42 and 48 months after frontline ASCT (Patients #4 and #5 on Table 1) and one relapsing 47 months after frontline syngeneic transplant (Patient #3). GVHD was questioned in 2 patients (Patients #3 and #5), both receiving allogeneic-like conditioning and cyclosporine prophylaxis. Two of nine patients developed a secondary cancer during follow up (Patient #5 myelodysplastic syndrome 7 years post-syngeneic transplant; Patient #4 transitional cell carcinoma 11 years post-syngeneic transplant). [Extracted from the article]

Soon after the anti-CD20 monoclonal antibody rituximab began to change the management of indolent and aggressive B cell lymphomas, development of alternative antibodies – including chemoimmunoconjugates – was undertaken. Among humanized and fully human CD20 antibodies, obinutuzumab has emerged as one antibody that seems to have lived up to the promise of improved efficacy based on in vitro and preclinical experiments. The data available, thus, far establish obinutuzumab's preferred role as the anti-CD20 antibody of choice in chronic lymphocytic leukemia and untreated follicular lymphoma, as well as an important addition to the treatment of rituximab-refractory indolent lymphomas. Additional trials in aggressive lymphoma are required to define the place of this new antibody in the management of patients with curable lymphoma subtypes. There are greater toxicities associated with this treatment, including increased infusion-related reactions and cytopenias, but these are manageable with standard supportive care measures. [ABSTRACT FROM AUTHOR]

Background: The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. Study Design and Methods: We conducted a pilot randomized multi‐center study of two transfusion algorithms (liberal, to maintain Hb 110–120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105–110 g/L vs. restrictive, 85–105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre‐transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety. Results: Twenty‐eight patients were randomized between February 2015–2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre‐transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p <.0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12‐week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre‐transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains. Conclusion: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients. [ABSTRACT FROM AUTHOR]

The standard treatment for Diffuse Large B-Cell Lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). However, many patients require subsequent treatment after relapsed disease. The ABC subtype of DLBCL (ABC-DLBCL) has a worse prognosis, and the PHOENIX trial explored adding ibrutinib to RCHOP for this patient population. The trial showed favorable outcomes for younger patients, and our study aimed to inform clinical decision-making via a cost-effectiveness model to compare RCHOP with and without ibrutinib (I-RCHOP). A Markov decision analysis model was designed to compare the treatments for patients younger than 60 years with ABC-DLBCL. The model considered treatment pathways, adverse events, relapses, and death, incorporating data on salvage treatments and novel therapies. The results indicated that I-RCHOP was more cost-effective, with greater quality-adjusted life years (QALY, 15.48 years vs. 14.25 years) and an incremental cost-effectiveness ratio (ICER) of CAD 34,111.45/QALY compared to RCHOP only. Sensitivity analyses confirmed the model's robustness. Considering the high market price for ibrutinib, I-RCHOP may be more costly. However, it is suggested as the preferred cost-effective strategy for younger patients due to its benefits in adverse events, overall survival, and quality of life. The decision analytic model provided relevant and robust results to inform clinical decision-making. [ABSTRACT FROM AUTHOR]

BACKGROUND A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. METHODS A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RESULTS RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. CONCLUSIONS RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon. Cancer 2015;121:2637-2645. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is common (40-65%) and potentially serious in myelodysplastic syndromes ( MDS). A systematic review was conducted to determine the safety and efficacy of adding a thrombopoietin-receptor ( THPO-R) agonist to standard MDS treatment. MEDLINE, EMBASE and CENTRAL databases were searched. We included randomized controlled trials comparing a THPO-R agonist to placebo. A meta-analysis of the effects was performed. Endpoints included bleeding and platelet transfusion rates, risk of progression to acute myeloid leukaemia ( AML) and mortality. Three hundred and eighty four patients from five trials were included, four using romiplostim and one using eltrombopag. Overall, the relative risk ( RR) of bleeding with romiplostim versus placebo was 0·84 [95% confidence interval ( CI): 0·57-1·24]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate ( RR 0·92; 95% CI: 0·86-0·99), as well as the exposure-adjusted platelet transfusion rate ( RR 0·69; 95% CI: 0·53-0·88). The RR of AML progression with romiplostim was 1·36 (95% CI: 0·54-3·40), however the outcome data were judged as higher risk of bias. Romiplostim is promising in its ability to decrease patient-important outcomes: bleeding and platelet transfusion need. Although the risk of AML progression was not increased, due to unclear risk of bias in the data, this safety concern is difficult to assess. Therefore, romiplostim cannot yet be routinely recommended. Early eltrombopag data is promising. [ABSTRACT FROM AUTHOR]

Simple Summary: Hodgkin lymphoma is the most common malignancy of the lymphatic system, usually affecting young people and with favorable response to treatment. Tailored treatment is important in this patient population to achieve good therapy response while not exposing them to higher treatment related toxicity. These patients undergone PET/CT studies at baseline for staging as part of their workup. PET/CT is an hybrid modality including morphological and molecular images and most of the Hodgkin lymphomas are radiotracer avid. Radiomics is a new field analyzing features within the images itself which are not visible to the naked eye. Our hypothesis was that some radiomics features in the PET or CT modality when combined with clinical variables (laboratory, type of tumor, etc.) may help in prediction of how patients would respond to therapy, risk of relapse and if they might need to have additional therapies. Purpose: The aim of the study is to evaluate the prognostic value of a joint evaluation of PET and CT radiomics combined with standard clinical parameters in patients with HL. Methods: Overall, 88 patients (42 female and 46 male) with a median age of 43.3 (range 21–85 years) were included. Textural analysis of the PET/CT images was performed using freely available software (LIFE X). 65 radiomic features (RF) were evaluated. Univariate and multivariate models were used to determine the value of clinical characteristics and FDG PET/CT radiomics in outcome prediction. In addition, a binary logistic regression model was used to determine potential predictors for radiotherapy treatment and odds ratios (OR), with 95% confidence intervals (CI) reported. Features relevant to survival outcomes were assessed using Cox proportional hazards to calculate hazard ratios with 95% CI. Results: albumin (p = 0.034) + ALP (p = 0.028) + CT radiomic feature GLRLM GLNU mean (p = 0.012) (Area under the curve (AUC): 95% CI (86.9; 100.0)—Brier score: 3.9, 95% CI (0.1; 7.8) remained significant independent predictors for PFS outcome. PET-SHAPE Sphericity (p = 0.033); CT grey-level zone length matrix with high gray-level zone emphasis (GLZLM SZHGE mean (p = 0.028)); PARAMS XSpatial Resampling (p = 0.0091) as well as hemoglobin results (p = 0.016) remained as independent factors in the final model for a binary outcome as predictors of the need for radiotherapy (AUC = 0.79). Conclusion: We evaluated the value of baseline clinical parameters as well as combined PET and CT radiomics in HL patients for survival and the prediction of the need for radiotherapy treatment. We found that different combinations of all three factors/features were independently predictive of the here evaluated endpoints. [ABSTRACT FROM AUTHOR]

In immunocompetent patients with primary central nervous system ( CNS) lymphoma, combined modality therapy ( CMT) using high-dose methotrexate and whole brain radiotherapy has improved response rates compared to chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity. A Markov decision-analytic model compared CMT to chemotherapy alone in patients with primary CNS lymphoma. Baseline probabilities were derived from a systematic literature review. Outcomes were life expectancy and quality-adjusted life expectancy. Sensitivity analyses were performed. The life expectancy was 2·69 years for CMT and 2·77 years for chemotherapy alone. The quality-adjusted life expectancies for the two strategies were 1·70 and 1·67 quality-adjusted life years ( QALYs) respectively. In younger patients <60 years of age, CMT yielded a quality-adjusted life expectancy of 2·71 QALYs, compared to 2·09 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0·62 QALYs or 7·4 quality-adjusted months. There was no difference between the strategies in the older group. The model was robust to key variables for the younger group. The preferred induction strategy for younger patients appears to be CMT, maximizing life expectancy, and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone. [ABSTRACT FROM AUTHOR]

AbstractThe prevalence of frailty in clinical trials of lymphoma is unknown. We conducted a secondary analysis of the phase III LY.12 trial in which patients with relapsed aggressive non-Hodgkin lymphoma were randomized to different salvage regimens before autologous stem cell transplant. The primary objective was to construct a lymphoma clinical trials-specific frailty index (LyFI) using previously described methods. The secondary objective was to describe the association of frailty withover all and event-free survival (OS, EFS). The LyFI was constructed using 619 patients, and11% (N = 70) were classified as frail. Frailty was associated with EFS (HR 1.94, 95%CI 1.53–2.46) and OS (HR 2.01, 95%CI 1.57–2.58) in univariable analysis, but was only significant as a continuous (not binary) variable in multivariable analysis controlling for prognostic score, suggesting limitations of a FI in this trial population. Future work could validate the FI using clinical assessments and/or apply it to an older trial population. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy and autologous stem cell transplant (ASCT) remains a cornerstone of treatment in relapsed/refractory (R/R) aggressive-histology lymphomas. This retrospective study examined efficacy and safety of peripheral blood stem cell (PBSC) mobilization using cyclophosphamide/etoposide and GCSF (CE + GCSF, n = 129) versus gemcitabine, dexamethasone and cisplatin and GCSF (GDP + GCSF, n = 210). All patients received first salvage with GDP. Patients mobilized with CE + GCSF required fewer days of leukapheresis (median 1 vs 2 day; p =.001) and achieved higher total CD34+ yield than GDP + GCSF patients (8.5 vs 7.1 × 106 CD34+ cells/kg, p =.001). Rates of febrile neutropenia and CD34+ collection ≥5 × 106 CD34+ cells/kg were similar (OR 1.19, 95% CI: 0.54–2.6, p =.66). In multivariable analysis, days to engraftment and admission duration were not statistically different between the two mobilization strategies. While CE + GCSF appeared more efficacious for mobilization after GDP salvage, this did not translate to significant differences in clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000–2009) and later (2010–2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada. [ABSTRACT FROM AUTHOR]

Background Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking. Methods We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates. Results We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P  = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P  = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P  = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P  < .0001). Conclusions Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality. [ABSTRACT FROM AUTHOR]

Summary: Bendamustine (B) with rituximab (R) has become the preferred regimen for patients with indolent lymphoma in Ontario, Canada, compared to R with cyclophosphamide, vincristine, prednisone (CVP) or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). We conducted a propensity‐matched retrospective cohort population‐based study of patients treated with R‐CVP/CHOP from 2005 to 2012 and patients treated with BR from 2013 to 2018. The primary outcome was 5‐year overall survival (OS), and secondary outcomes included toxicities and healthcare utilization. The 5‐year OS for patients treated with BR (n = 2023) and R‐CVP/CHOP (n = 2023) was 80% and 75% respectively. Treatment with BR was associated with improved OS (HR 0.79, 95% CI 0.69–0.91). During the first 9 months, patients treated with BR versus R‐CVP/CHOP had a higher number of admissions for infection (22% compared to 17%, p < 0.01) and a higher number of mean ED visits (mean 1.01 ± 1.68 visits vs. 0.85 ± 1.51 visits, p < 0.01). This trend persisted for 3 years. The adjusted 5‐year OS for patients 75 years and older did not differ based on treatment regimen (55.5% for BR vs. 55.4% for R‐CVP/CHOP). Our study supports the use of BR for patients with indolent lymphoma requiring treatment but suggests increased risk of certain toxicities warranting careful patient selection. [ABSTRACT FROM AUTHOR]

Early-stage Hodgkin lymphoma has become one of the most curable hematologic malignancies. Depending upon the disease location, possible toxicities, and patient preference, chemotherapy alone with ABVD remains an accepted treatment modality for this disease. There remains a paucity of data regarding the longitudinal trajectory of health-related quality of life (HRQoL) in patients treated for HL. The impact of disease and treatment on HRQoL is increasingly important to understand as the number of long-term survivors increases. We report the longitudinal HRQoL using data prospectively collected from diagnosis up to 10 years post-treatment in the ABVD arm of the HD.6 randomized controlled trial for early-stage HL patients (N=169). We analyzed HRQoL using the EORTC QLQ-C30 collected at baseline, 3 months, 6 months, and 12 months after completion of chemotherapy and yearly up to year 10. Clinically and statistically significant improvements were noted for specific domains including emotional (3 months post-treatment), social (12 months post-treatment) and financial functioning (2 years post-treatment), and the specific symptom of fatigue (6 months post-treatment) during the follow-up period. To our knowledge, this is the first prospective, longitudinal analysis of HRQoL specifically among patients with early-stage HL treated with ABVD therapy alone. Although improvements were noted, sustained clinically and statistically significant improvements were noted only in select symptoms emphasizing the need to better understand and optimize HRQoL among this patient group. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 46-year-old woman who was presented to the emergency department with weakness in her limbs and was eventually diagnosed with diffuse large B-cell lymphoma (DLBCL).

Marginal zone lymphomas (MZL) are a rare, heterogenous group of lymphomas, accounting for 5–17% of indolent non-Hodgkin lymphomas in the western world. They can be further divided into three subtypes: extranodal MZL, splenic MZL, and nodal MZL. These subtypes differ in clinical presentation and behavior, which influences how they are managed. There is currently no standard of care for the treatment of MZL, owing to the difficulty in conducting phase 3 randomized trials in MZL, and the fact that there are limited data on the efficacy of therapy in individual subtypes. Treatment practices are thus largely borrowed from other indolent lymphomas and are based on patient and disease characteristics, as well as access to therapy. This review summarizes the Canadian treatment landscape for MZL and how these therapies may be sequenced in practice. [ABSTRACT FROM AUTHOR]

Patients with hematological malignancies (HM) are at risk of acute respiratory failure (ARF). Malnutrition, a common association with HM, has the potential to influence ICU outcomes. Geriatric nutritional risk index (G-NRI) is a score derived from albumin and weight, which reflects risk of protein-energy malnutrition. We evaluated the association between G-NRI at ICU admission and ICU mortality in HM patients with ARF. We conducted a single center retrospective study of ventilated HM patients between 2014 and 2018. We calculated G-NRI for all patients using their ICU admission albumin and weight. Our primary outcome was ICU mortality. Secondary outcomes included duration of mechanical ventilation and ICU length of stay. Two hundred eighty patients were admitted to the ICU requiring ventilation. Median age was 62 years (IQR 51–68), 42% (n = 118) were females, and median SOFA score was 11 (IQR 9–14). The most common type of HM was acute leukemia (54%) and 40% underwent hematopoietic cell transplant. Median G-NRI was 87 (IQR 79–99). ICU mortality was 51% (n = 143) with a median duration of ventilation of 4 days (IQR 2–7). Mortality across those at severe malnutrition (NRI < 83.5) was 59% (65/111) compared to 46% (76/164) across those with moderate-no risk (p = 0.047). On multivariable analysis, severe NRI (OR 2.34, 95% CI 1.04–5.27, p = 0.04) was significantly associated with ICU mortality. In this single center, exploratory study, severe G-NRI was prognostic of ICU mortality in HM patients admitted with respiratory failure. [ABSTRACT FROM AUTHOR]

Interim imaging with computed tomography (iCT) to assess response is common during frontline chemoimmunotherapy for follicular lymphoma (FL), but there is little evidence of its utility. We retrospectively reviewed outcomes of iCT in 190 patients with biopsy-proven FL who received first-line chemoimmunotherapy from 2003–2018. Most iCTs showed partial response (PR, 83%), with a minority showing complete response (CR, 8%) or stable disease (5%). Seven patients (4%) had radiographic disease progression (PD) on iCT; on repeat biopsy, four had another malignancy identified and three had transformation to DLBCL. Only one had asymptomatic PD. The 3-year PFS of all patients was 74% (median follow up 75 months). Patients with PR on iCT had similar 3-year PFS and OS as those with CR. In conclusion, iCT has limited utility in identifying patients with asymptomatic early progression during first-line treatment. Patients with PD mid-treatment warrant biopsy to identify histologic transformation or other malignancies. [ABSTRACT FROM AUTHOR]

Selinexor is a first-in-class, oral therapy that selectively inhibits nuclear export. The drug is active with an overall response rate (ORR) of approximately 30% in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL). Long-term patient follow-up has not been reported. Thirty-one NHL patients were treated between July 2012 and July 2018; 22 were evaluated for response. ORR was 32% (7/22). Two patients achieved complete remission (CR) and were alive and lymphoma-free at the end of follow-up. Fifteen patients (68%) progressed during treatment, most of them died within 3–10 months. The most common grade 3/4 adverse events were gastrointestinal and hematological. Median follow up was 50 months. Overall survival for the entire cohort was 16%. Selinexor monotherapy for r/r NHL is an active therapy with the potential for long-term disease control. It may serve as a 'bridge' to subsequent therapy. Additional studies are needed to identify predictive biomarkers and to evaluate combination approaches. [ABSTRACT FROM AUTHOR]

The main objective of treatment in systemic light chain amyloidosis (AL amyloidosis) is to achieve the best hematological response. Deeper responses are associated with better organ responses and survival. In this study, we analysed the efficacy of prolonged duration treatment after first line in patients with AL amyloidosis. Retrospective analysis that included patients older than 18 years with AL amyloidosis. We excluded patients with more than 30% marrow plasmacytosis or concurrent multiple myeloma. Two cohorts identified accordingly if they received or not prolonged treatment after the first line. Survival analysis regarding progression free survival (PFS) and overall survival (OS) estimated with Kaplan–Meier and comparisons between groups with log-rank. Thirty-eight patients were included in the analysis with a median age of 55 years. Twenty-one patients received prolonged duration treatment and 17 did not. In the prolonged duration group, after a median duration of 12 months, the median PFS was 58.8 months. In the fixed duration treatment group, PFS was 30.6 months. The difference was significant with p =.0045 favouring prolonged duration treatment. Organ response was sustained for a longer period in the prolonged duration treatment group. For OS, the difference was not significant. Prolonged duration treatment in patients with systemic light chain amyloidosis correlated with better PFS and deeper organ responses. Prospective studies are needed to analyse this further. [ABSTRACT FROM AUTHOR]

Objectives: The prognostic value of kinetics of response to multiple myeloma (MM) therapy is controversial. We aimed to expand the knowledge on this topic by reviewing the kinetics of response to both first‐ and second‐line MM therapy, utilizing a homogeneously treated cohort and analyzing separately both M‐spike and light chain (LC) responses for each patient. Methods: We reviewed all patients who received first‐line cyclophosphamide, bortezomib and dexamethasone induction followed by autologous transplant with melphalan and lenalidomide maintenance in our center between 2007 and 2019. Results: Analyzing 360 patients, we observed no correlation between response kinetics to first‐ versus second‐line therapy at the individual patient level. Time to best response to first‐line therapy was not a predictor of outcome; however, longer time to best response was highly predictive of a favorable outcome in the second‐line setting, independent of other factors. Patients with IgA‐MM cleared their M‐spike faster than IgG‐MM, probably reflecting different half‐lives of these isotypes rather than disease biology, as the clearance of LC in both subtypes was similar. Conclusions: Analyzing both M‐spike and LC responses in a homogenously treated cohort, we identified important insights regarding the prognostic value of kinetic patterns. Prospective analysis may shed more light on unsolved questions. [ABSTRACT FROM AUTHOR]

There is increasing interest from cancer patients and their healthcare providers in the use of virtual care in routine clinical practice. In the setting of hematologic malignancy, where patients often undergo complex and immunodepleting treatments, understanding how to use virtual care safely and effectively is critically important. We aimed to describe the use of virtual care in patients with hematologic malignancies and to examine physician- and patient-reported outcomes in the form of a systematic scoping review. An electronic search of PubMed, Ovid MEDLINE, Elsevier Embase, Scopus, and EBSCO CINAHL was conducted from January 2000 to April 2021. A comprehensive search strategy was used to identify relevant articles, and data were extracted to assess the study design, population, setting, patient characteristics, virtual care platform, and study results. Studies were included if they described the use of virtual care for patients with hematologic malignancies; commentaries were excluded. Fifteen studies met the inclusion criteria after abstract and full-text review. Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts for more urgent follow-up. Four studies described the use of phone-based interventions. Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, especially when patients were experiencing side-effects or had questions about their treatment. Overall, the use of virtual care in patients with hematologic malignancies appears feasible, and resulted in high patient satisfaction. Further research is needed in order to evaluate the optimal method of integrating virtual care into clinical practice. [ABSTRACT FROM AUTHOR]

Summary: Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma‐related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high‐risk by the RHL30 assay had inferior failure‐free survival (FFS) after autologous stem cell transplantation (2‐year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk‐stratifies patients considered for autologous stem cell transplantation. [ABSTRACT FROM AUTHOR]

Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI. [ABSTRACT FROM AUTHOR]

Buparlisib is an orally available pan-Class I PI3K inhibitor, that is more potent than idelalisib in vitro. Its distinct toxicities include hyperglycemia, hypertension, and mood disturbance. IND216 is a single arm phase II trial of buparlisib in Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Fourteen patients were enrolled, 13 were evaluable for response and toxicity. Six of 13 patients had a partial response (46%) with a median duration of response of 15.5 months, all 11 patients with tumor assessment experienced tumor shrinkage. The most common adverse events (≥15%) were hyperglycemia, fatigue, anxiety, and gastrointestinal toxicities; all were < grade 3 except for fatigue. Three patients stopped therapy for alterations in mood. Lower levels of raptor were significantly associated with greater tumor shrinkage, suggesting that raptor could be a biomarker for response. This requires further validation in a larger CLL patient cohort. The clinical activity of buparlisib is comparable to other phosphatidylinositol-3-kinase inhibitors, with a different toxicity profile. Buparlisib, an oral, pan PI3 kinase inhibitor, is associated with a 46% partial response rate among patients with relapse chronic lymphocytic leukemia (CLL). This is a similar clinical activity to other phosphatidylinositol-3-kinase inhibitors tested. However, buparlisib has a distinct toxicity profile, characterized by hyperglycemia, hypertension, and mood alteration. In agreement with our previous preclinical study, our results suggest that basal raptor expression in CLL correlates with clinical response to buparlisib. [ABSTRACT FROM AUTHOR]

Summary: Post‐transplant lymphoproliferative disorder (PTLD) may arise after solid organ transplantation, and the most common subtype resembles diffuse large B cell lymphoma (DLBCL). In DLBCL‐type PTLD, the anti‐CD20 antibody rituximab (R) may be combined with chemotherapy (R‐CHOP) or use a strategy (R‐primary; similar to the PTLD‐1 clinical trial) consisting of induction with four weekly doses of R‐alone, without any chemotherapy or sequential R‐CHOP follow‐up. Here we report on a multicentre retrospective cohort of solid organ transplant patients with DLBCL‐type PTLD that were treated with R. In 168 adults, two‐year overall survival (OS) was 63·7% [95% CI (confidence interval) 56·6–71·7%]. No difference in OS was observed, whether patients were treated with R‐CHOP versus the R‐primary strategy. In the 109 patients treated with R‐primary, multivariate analysis found that baseline IPI score and the response to R‐induction predicted OS. Patients who responded to R‐induction had durable remissions without the addition of chemotherapy. Conversely, of the 46 patients who had stable or progressive disease after R‐induction (R‐failure), those who received R‐CHOP had an only marginally improved outcome, with a two‐year OS of 45% (23·1–65·3%) vs. no R‐CHOP at 32% (14·7–49·8%). In real‐world patients, R‐failure and high IPI scores predict a poor outcome in DLBCL‐type PTLD. [ABSTRACT FROM AUTHOR]

Outcomes of patients with relapsed low-grade lymphoma retreated with rituximab are similar to rituximab naïve patients Rituximab combined with chemotherapy has been shown to be superior to chemotherapy alone in patients with relapsed/refractory indolent lymphomas [[1]]. As per the regional funding guidelines, patients had to have at least a one-year treatment-free period between their first- and second-line therapies; this therefore excluded any patients who were refractory to rituximab per this definition. Maintenance rituximab use after second-line chemoimmunotherapy was associated with superior PFS (HR: 0.39 (95%CI: 0.2, 0.77), I p i =.0069), with most patients (19/26 patients, 73%) who received it being in Group 1 (NoR-R). [Extracted from the article]

The precise role of radiation therapy in primary central nervous system lymphoma (PCNSL) remains controversial. We reviewed the records of all patients treated for PCNSL at our center between 2004 and 2015. A total of 103 patients treated with either chemotherapy alone (n = 30), radiotherapy alone (n = 36), or combined-modality treatment (n = 37) were analyzed. The median progression-free survival (PFS) and overall survival (OS) were 13.9 and 20.9 months, respectively. Of those who received chemotherapy, 52.2% achieved complete response/ unconfirmed complete response (CR/Cru) after induction; a trend for improved PFS was observed for those who received consolidation WBRT (NR vs. 30.1 months, p = .092) but not OS (NR vs. 31.6 months, p = .283). Patients who achieved a partial response with chemotherapy and proceeded with WBRT had a similar long-term survival to those who achieved CR/CRu with chemotherapy without WBRT (PFS 15.2 vs. 30.1 months, p = .888; OS 22.0 vs. 31.6 months, p = .340). Consolidation WBRT improved PFS, but not OS, and this must be balanced against possible risks of neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Brentuximab vedotin is currently approved for patients with relapsed or refractory Hodgkin's lymphoma who previously received an autologous stem cell transplant or two previous multiagent chemotherapy regimens, and for patients with relapsed or refractory systemic anaplastic large-T-cell lymphoma who previously received at least one chemotherapy regimen. A high proportion of patients with CD30-expressing relapsed or refractory lymphomas have durable responses to single-agent brentuximab vedotin and show longer progression-free survival than do patients treated with chemotherapy. In patients with Hodgkin's lymphoma and peripheral T-cell lymphoma, treatment with bendamustine alone only achieves modest improvements in progression-free survival compared with that for chemotherapy. The objective of this study was to explore the safety and clinical activity of the combination of brentuximab vedotin plus bendamustine in heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma and anaplastic large-T-cell lymphoma.Methods: In this international, multicentre, single-arm, phase 1-2 trial, eligible patients were aged 18 years or older, had histologically confirmed relapsed or refractory Hodgkin's lymphoma or anaplastic large-T-cell lymphoma, had biopsy-proven CD30-positive tumours, had an Eastern Cooperative Oncology Group performance status of 2 or less, and received at least one previous multiagent chemotherapy regimen. In phase 1, patients were assigned following a 3+3 dose-escalation design to one of four cohorts to receive one dose of either 1·2 mg/kg or 1·8 mg/kg of brentuximab vedotin intravenously on day 1 of a 21 day cycle, plus one dose of bendamustine (70 mg/m2, 80 mg/m2, or 90 mg/m2) on days 1 and 2 of the treatment cycle. In phase 2, all patients were assigned to receive brentuximab vedotin plus bendamustine at the recommended phase 2 dose from phase 1. The primary endpoints were maximum tolerated dose and dose-limiting toxicity for phase 1, and the proportion of patients achieving an overall response in phase 2. For both phases 1 and 2, all patients receiving at least one dose of study drug were evaluable for toxicity and all patients completing at least one cycle of therapy were evaluable for response. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01657331.Findings: Between July 26, 2012, and May 31, 2017, we enrolled and assigned 65 patients to treatment (64 [98%] with Hodgkin's lymphoma and one [2%] with anaplastic large-T-cell lymphoma; 28 [43%] during phase 1 and 37 [57%] during phase 2). In the phase 1 part, the maximum tolerated dose of the combination was not reached. Dose-limiting toxicities were observed in three (11%) of 28 patients, including grade 4 neutropenia at 1·8 mg/kg brentuximab vedotin plus 80 mg/m2 of bendamustine in two (7%) patients and diffuse rash at 1·2 mg/kg brentuximab vedotin plus 70 mg/m2 of bendamustine in one (4%) patient. The recommended phase 2 dose was deemed to be 1·8 mg/kg of brentuximab vedotin and 90 mg/m2 of bendamustine, which are the standard doses of the drugs when given as single agents. In the phase 2 part, an overall response was achieved in 29 (78% [95% CI 62-91]) of 37 patients. Serious adverse events included grade 3 lung infection in five (14%) of 37 patients in the phase 2, and grade 3-4 neutropenia in 16 (25%) of 65 patients across phases 1 and 2. There were no treatment-related deaths.Interpretation: This study shows that brentuximab vedotin plus bendamustine, with a favourable safety profile, is an active salvage regimen for heavily pretreated patients with relapsed or refractory Hodgkin's lymphoma. This salvage regimen can potentially serve as an efficacious and safe alternative to platinum-based chemotherapy before autologous stem cell transplant.Funding: Seattle Genetics, Lymphoma Research Fund of Columbia University and National Center for Advancing Translational Sciences, and National Institutes of Health. [ABSTRACT FROM AUTHOR]

Increasing accessibility of fertility preservation (FP) options has permitted women to retain fertility following anticancer therapies. Several published guidelines have made recommendations for FP however their implementation into practice is currently unknown. In this review, we aim to provide oncology clinicians practical information about FP options for post-pubescent female cancer patients and recommendations for care delivery in order to answer preliminary questions and help triage whether FP referral is appropriate. Herein, we present a resource for oncology providers to guide them with FP discussions. Key points that are discussed in this critical review include: i) All cancer patients beginning a new plan of care should be informed of potential fertility risk. ii) If a woman requests further information on FP interventions, referral to a FP clinic should be made. iii) Given the evolving technologies in this area, patients should be informed of those which are proven and unproven, with oocyte and embryo preservation recognized as standard practice. iv) Random start (independent of menstrual cycle day) techniques are available to minimize oncologic treatment delays. v) Specific protocols for ovarian stimulation may be center-specific. vi) There is unlikely an increased cancer recurrence risk as a result of stimulation protocols in women with hormone-sensitive cancers. vii) Lastly, given the absence of consensus in the literature, routine use of GnRH analogs is not recommended for all cancer patients, however may be considered in select cases, such as high-risk women in whom definitive FP is not possible or feasible. [ABSTRACT FROM AUTHOR]

Purpose Cancer drug wastage occurs when a parenteral drug within a fixed vial is not administered fully to a patient. This study investigated the extent of drug wastage, the financial impact on the hospital budget, and the cost savings associated with current mitigation strategies. Methods We conducted a cross-sectional study in three University of Toronto-affiliated hospitals of various sizes. We recorded the actual amount of drug wasted over a 2-week period while using current mitigation strategies. Single-dose vial cancer drugs with the highest wastage potentials were identified (14 drugs). To calculate the hypothetical drug wastage with no mitigation strategies, we determined how many vials of drugs would be needed to fill a single prescription. Results The total drug costs over the 2weeks ranged from$50,257 to $716,983 in the three institutions. With existing mitigation strategies, the actual drug wastage over the 2 weeks ranged from $928 to $5,472, which was approximately 1% to 2% of the total drug costs. In the hypothetical model with no mitigation strategies implemented, the projected drug cost wastage would have been $11,232 to $149,131, which accounted for 16% to 18% of the total drug costs. As a result, the potential annual savings while using current mitigation strategies range from 15% to 17%. Conclusion The financial impact of drug wastage is substantial. Mitigation strategies lead to substantial cost savings, with the opportunity to reinvest those savings. More research is needed to determine the appropriate methods to minimize risk to patients while using the cost-saving mitigation strategies. [ABSTRACT FROM AUTHOR]

We evaluated 52 patients with myelodysplastic syndrome (MDS) who had received at least one red blood cell (RBC) transfusion. In the 4-week period following the first transfusion, 24 patients (group 1) required no transfusion, while 28 (group 2) required transfusion of two or more units of RBCs. Survival was greater in group 1 (440 weeks vs. 167 weeks, p < 0.01), even when only international prognostic scoring system (IPSS) low and intermediate-1 risk patients were analyzed (median overall survival 491 vs. 170 weeks, p < 0.05), independent of age, IPSS and progression to acute myeloid leukemia (AML). The intensity of transfusion required in the first few weeks after the first transfusion predicts disease severity and correlates with survival. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66-year-old female who was diagnosed with myelodysplastic syndrome (MDS), with multilineage dysplasia and she was treated with prednisone and colchicine.