Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Efficacy and safety of idecabtagene vicleucel in patients with relapsed-refractory multiple myeloma not meeting the KarMMa-1 trial eligibility criteria: A real-world multicentre study.

Ide-cel received approval for relapsed-refractory multiple myeloma based on the results of the KarMMa-1 trial. However, patients with significant comorbidities, aggressive disease and prior B-cell maturation antigen-directed therapy (BCMA-DT) were excluded. This retrospective study evaluated real-world outcomes of patients who did not meet the KarMMa-1 eligibility criteria and were treated with standard of care (SOC) ide-cel. A total of 69 patients from three US centres who did not meet the KarMMa-1 criteria underwent ide-cel infusion. The main reasons for trial ineligibility included baseline grade 3-4 cytopenia (39%), prior BCMA-DT (26%), renal impairment (19%) and Eastern Cooperative Oncology Group performance status ≥2 (14.5%). Cytokine-release syndrome occurred in 81% vs. 84%, and immune effector cell-associated neurotoxicity syndrome occurred in 28% vs. 18% of SOC versus KarMMa-1 patients, respectively. Early infection (≤8 weeks post-infusion) and severe infection rates were 42% vs. 49% and 30% vs. 22% for the SOC versus KarMMa-1 cohorts, respectively. Grade 3-4 cytopenias for SOC versus KarMMa-1 cohorts were: neutropenia (87% vs. 89%), anaemia (51% vs. 60%) and thrombocytopenia (65% vs. 52%). Overall response rate was higher for the SOC cohort (93% vs. 73%), as was the complete response or better rate (48% vs. 33%). However, median progression-free survival and overall survival were comparable between the two groups. Our findings support broadening the inclusion criteria of future trials evaluating ide-cel.

Comparison of biosimilar filgrastim and originator filgrastim for peripheral blood stem cell mobilization for allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Nivestym, a biosimilar granulocyte colony-stimulating factor (G-CSF) to the originator filgrastim (Neupogen), is now being used for the mobilization of peripheral blood stem cells (PBSC) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to compare the efficacy of Nivestym and Neupogen for PBSC mobilization in healthy allogeneic donors. METHODS: We conducted a retrospective single-center study including 541 adult allo-HSCT donors receiving Nivestym (January 2013-July 2020), or Neupogen (July 2020-June 2023) for donor PBSC mobilization. Bivariate analysis was conducted using SPSS version 28. Statistical significance was determined at a p-value <.05. RESULTS: Our study included 541 allo-HSCT donors who received Neupogen (n = 345, 64%) or Nivestym (n = 196, 36%) for PBSC mobilization. The median age was 47 years (range 17-76). The median donor weight was 86 kg (95% confidence interval [CI]: 87-91). Donors receiving Neupogen had similar pre-G-CSF white blood cell count, CD34+ percentages, and circulating CD34+ count compared with donors receiving Nivestym. The Neupogen group had similar median PBSC product total neutrophil count, CD34+ percentage, absolute CD34+ count, and infused CD34+ dose compared with the Nivestym group. For donors aged 35 years or younger, the median CD34+ dose was higher in donors who received Neupogen compared with Nivestym (6.9 vs. 6.3 million cells/kg, p = .044). CONCLUSIONS: Nivestym demonstrated similar efficacy for PBSC mobilization compared with Neupogen among allo-HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34+ count was noted with Nivestym compared with Neupogen.

Safety and efficacy of B cell maturation antigen-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma and concurrent light chain amyloidosis.

Clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma (RRMM) have typically excluded patients with AL amyloidosis. As a result, there are limited data on the safety and efficacy of CAR T-cell therapy in this patient population. We retrospectively reviewed eight consecutive patients with RRMM and AL amyloidosis who were treated with standard of care CAR T-cell therapy. Cytokine release syndrome was seen in 75% of patients (grade ≥3: 0%) and immune effector cell-associated neurotoxicity syndrome (grade 1) in only one patient. Low-grade cytopenias were common (any grade/grade ≥3: neutropenia 62.5%/37.5%, anemia 37.5%/0%, thrombocytopenia 25%/0%). CAR T-cell therapy led to rapid and deep responses with a median time to best response of 43 days and a hematologic very good partial response or better rate of 62.5%. Overall, we found that commercial CAR T-cell therapy was feasible, and effective in patients with RRMM and concurrent AL amyloidosis.

Safety and efficacy of eltrombopag in patients with post-CAR T cytopenias.

BACKGROUND: While chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment outcomes of relapsed/refractory hematological malignancies, this therapy is associated with post-treatment cytopenias, which can pose a challenge to its safe administration. This study describes the management of post-CAR T cytopenias using the thrombopoietin mimetic eltrombopag. METHODS: This retrospective analysis included adult patients with lymphoma or myeloma who received CAR T-cell therapy at two academic medical centers. Eltrombopag was initiated for patients who had persistent high-grade leukopenia and/or thrombocytopenia beyond 21 days post-CAR T infusion. Risk factors and outcomes were assessed and compared for patients who did or did not receive eltrombopag. RESULTS: Among the 185 patients analyzed, a majority (88%) experienced thrombocytopenia or leukopenia at day +30 post-CAR T infusion. A total of 42 patients met the criteria for eltrombopag treatment and initiated therapy. Patients who received eltrombopag were more likely to have pre-existing cytopenias at lymphodepletion, receive bridging therapy, experience an infection, or require intensive care. Recovery from cytopenias occurred within 180 days for a majority (94%) of patients. CONCLUSIONS: The use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered safe without any significant toxicities. The use of eltrombopag for post-CAR T cytopenias might be effective in a high-risk patient population but requires further study.

Efficacy and safety of daratumumab, pomalidomide, and dexamethasone versus daratumumab, carfilzomib, and dexamethasone in daratumumab-naïve relapsed multiple myeloma.

OBJECTIVES AND METHODS: We conducted a multicenter retrospective study to analyze the safety and efficacy of DPd versus DKd in daratumumab naïve RRMM patients treated in real-world practice. RESULTS: A total of 187 patients with RRMM were included in the analysis; 128 patients received DPd, and 59 patients received DKd. A vast majority (80%) of patients had lenalidomide refractory disease and nearly 50% had bortezomib refractory disease. The overall response and complete response rates were 76% and 34% in the DPd group versus 80% and 51% in the DKd group, respectively. With a median follow up of 36 months for the entire patient population, median PFS and OS in the DPd versus DKd groups were 12, 12, 37, and 35 months, respectively. The most common grade 3+ adverse events in the DPd versus DKd groups were neutropenia (32% vs. 7%), anemia (14% vs. 10%), thrombocytopenia (13% vs. 15%), and cardiovascular events (4% vs. 15%), respectively. Both DPd and DKd appeared to be a safe and effective treatment options for RRMM. CONCLUSIONS: While there were more cytopenias associated with DPd and more cardiovascular side effects with DKd, there were no significant differences in the survival outcomes with these two regimens.

Single-agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM-2 trial.

BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) have a high unmet treatment need. Belantamab mafodotin (belamaf), a first-in-class, B-cell maturation antigen-binding antibody-drug conjugate, eliminates myeloma cells through direct cell killing and an anti-myeloma immune response. METHODS: DREAMM-2 (NCT03525678) was a phase 2, two-arm, open-label trial in patients with heavily pretreated RRMM who had three or more prior therapies, were refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 monoclonal antibody. Belamaf was given at 2.5 or 3.4 mg/kg every 3 weeks. The primary end point was overall response rate (ORR); secondary end points included progression-free survival (PFS), overall survival (OS), safety, ocular symptoms, and health-related quality of life (HRQOL). RESULTS: This final analysis (cutoff date, March 31, 2022), N = 223, with median follow-up of 12.5 and 13.8 months, demonstrated an ORR of 32% and 35%, median PFS of 2.8 and 3.9 months, and median OS of 15.3 and 14.0 months in the 2.5 mg/kg and 3.4 mg/kg cohorts, respectively. Median duration of response was 12.5 and 6.2 months. No new safety signals were observed; the most common Grade 3 and 4 adverse events were keratopathy (29% vs. 25%), thrombocytopenia (22% vs. 29%), and anemia (21% vs. 28%). HRQOL outcomes suggest that overall global health status/quality of life, physical and role functioning, and overall disease symptoms were maintained or improved during treatment. CONCLUSIONS: This final analysis of DREAMM-2 confirms that in patients with triple-class refractory RRMM, single-agent belamaf results in durable and clinically meaningful responses with a manageable safety profile.

Time-to-event surrogate end-points in multiple myeloma randomised trials from 2005 to 2019: A surrogacy analysis.

Use of surrogate end-points such as progression-free survival (PFS) and other time-to-event (TTE) end-points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end-points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co-primary end-point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38-0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30-0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42-0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.

Clinical efficacy of retreatment of daratumumab-based therapy (D2) in daratumumab-refractory multiple myeloma.

Daratumumab demonstrates activity as a single agent and in combination with either immunomodulatory agents (IMiDs) or proteasome inhibitors (PIs) in relapsed refractory multiple myeloma (RRMM). However, little is known about the benefit of daratumumab retreatment in daratumumab-refractory MM. This study aimed to analyze the clinical efficacy of daratumumab-based retreatment (D2) in patients who are daratumumab refractory MM. Retrospectively, we identified 43 RRMM patients from a single-center database review. The median age was 65 years, 42% patients had high-risk cytogenetics, and 23% had an extramedullary disease, while the median time between D2 and prior daratumumab was 1 (0.25-39) month. All D2 patients received combination therapy with either pomalidomide, carfilzomib, bortezomib, or lenalidomide. The response rate, median progression-free, and overall survival were 49%, 7.97 and 32.6 months, respectively. Our study raises the possibility of re-utilizing daratumumab in combination with different classes of anti-myeloma drugs to generate responses in RRMM patients who are daratumumab-refractory.

Palliative care utilization, transfusion burden, and end-of-life care for patients with multiple myeloma.

INTRODUCTION: Despite treatment advances, multiple myeloma (MM) remains a significant source of morbidity and mortality. We aimed to examine specialist palliative care (SPC) involvement and end-of-life care for patients with MM. METHODS: We assessed all deceased patients with a diagnosis of MM who received care at a single institution from January 2010 to December 2019 and assessed SPC involvement. RESULTS: We reviewed 456 deceased patients. Overall, 207 patients (45.4%) received SPC visits by clinicians during their disease, and 153 (33.5%) were on MM treatment in the month before death. Median time from SPC consultation to death was 1 month, with 42 (9.2%) of patients receiving SPC visits 6 or more months before death. Amongst the patients for which a place of death was reported (351), 117 (33.3%) died in the acute care setting. Outpatient SPC did not correlate with a reduction of death in the acute care setting. In the group of patients who received outpatient SPC, 22/84 (26.2%) died in an acute care setting, whereas 95/267 (35.5%) patients who did not receive outpatient SPC also died in an acute care setting, (p = .11). CONCLUSION: In our analysis of the entire trajectory of the MM patient experience from diagnosis to death, we found low rates of SPC involvement and a significant proportion of patients receiving aggressive care at end-of-life. While there is no clear correlation that SPC involvement impacted the rate of acute care deaths or decreased utilization of MM treatment in the last month of life, further prospective research on optimal utilization of SPC is required.

Neutralizing antibody responses against SARS-CoV-2 in patients with plasma cell disorders who are on active treatment after two doses of mRNA vaccination.

Many patients with plasma cell disorder (PCD) on active treatment with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require hospitalization, with an increased mortality rate over healthy adults. The FDA approved two mRNA vaccines against SARS-CoV-2: BNT162b2 and mRNA-1273. To assess the efficacy of vaccination in patients with PCD, retrospectively, we identified all patients on active treatment. A total of 149 patients were included. Neutralizing antibodies (NAbs) levels against SARS-CoV-2 adequate, intermediate, and no response were observed in 42%, 32%, and 26%, respectively. Low NAbs were seen in patients on daratumumab combinations or anti-BCMA therapy, low lymphocytes, and low IgG levels. Twenty-three (15%) patients have SARS CoV-2, while 8% required hospitalization, majority of these patients had intermediate or no response based on NAbs levels. Therefore, checking NAbs may be clinically helpful in identifying patients' responses. Further prospective studies should ascertain the value of a third vaccine dose in this population.

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study.

BACKGROUND: On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg. METHODS: DREAMM-2 is an ongoing, phase 2, open-label, 2-arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti-CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee. RESULTS: As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty-one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%-43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression-free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6-3.6 months), respectively. Response and survival outcomes in patients who had high-risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow-up. CONCLUSIONS: Extended follow-up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM.

Hospitalization at the end of life in patients with multiple myeloma.

BACKGROUND: Despite advances in treatment, multiple myeloma (MM) remains incurable and results in significant morbidity and mortality. Further research investigating where MM patients die and characterization of end-of-life hospitalizations is needed. METHODS: We utilized the National Inpatient Sample (NIS) to explore the hospitalization burden of MM patients at the end of their lives. RESULTS: The percent of patients dying in the hospital as a percent of overall MM deaths ranged from 54% in 2002 to 41.4% in 2017 (p < 0.01). Blood transfusions were received in 32.7% of these hospitalizations and infections were present in 47.8% of patients. Palliative care and/or hospice consultations ranged from 5.3% in 2002 to 31.4% in 2017 (p < 0.01). CONCLUSION: Our study demonstrates that patients with MM dying in the hospital have a significant requirement for blood transfusions and have a high infection burden. We also show that palliative care and hospice involvement at the end of life has increased over time but remains low, and that ultimately, inpatient mortality has decreased over time, but MM patients die in the hospital at a higher rate than the general population.

Infection risks in multiple myeloma: a systematic review and meta-analysis of randomized trials from 2015 to 2019.

BACKGROUND: Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments. METHODS: We performed a systematic review to evaluate the monthly risk of grade III/IV infection, pneumonia, and neutropenia in patients with myeloma enrolled in randomized clinical trials (RCTs). RESULTS: The risk of grade III or higher infection, pneumonia, and neutropenia persists among all phases of treatment. There was no statistical difference in grade III or higher infection, pneumonia, and neutropenia between frontline and relapsed/refractory setting. In the maintenance setting, the complications of infection, pneumonia, and neutropenia were low, but not negligible. Three-drug regimens were no more likely than two-drug regimens to have an increased risk of Grade III or higher infection. CONCLUSIONS: This is the first study to quantify the monthly risk of grade III or higher infection, pneumonia, and neutropenia across different treatment regimens in the frontline, maintenance, and relapsed/refractory settings. The results of our systematic review demonstrate a significant risk for severe infection, pneumonia, and neutropenia in patients with MM. Further studies are needed to determine the value of antibiotic prophylaxis in a broader myeloma patient population, as well as other approaches that will further mitigate the morbidity and mortality related to infection in this vulnerable patient population.

Carfilzomib, cyclophosphamide, and dexamethasone (KCd) for the treatment of triple-class relapsed/refractory multiple myeloma (RRMM).

BACKGROUND: Multiple myeloma (MM) is an incurable hematologic malignancy, and outcomes remain poor for patients with triple-class relapsed/refractory MM (RRMM). Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes of the KCd on triple-class RRMM patients at our institution. PATIENTS AND METHODS: Twenty-three patients with triple-class RRMM treated with KCd between June 2017 and October 2020 were included in our analysis. The regimen KCd consisted of 28 days cycles of carfilzomib 20/36 mg/m2 IV on days 1, 2, 8, 9, 15, and 16, cyclophosphamide 300 mg/m2 IV weekly, and dexamethasone (20-40) mg orally weekly. RESULTS: Patients received a median of 6 (3-10) prior regimens. The median number of cycles administered was 4 (1-11) cycles. Overall response rate was 52%, 6 patients (26%) achieved very good partial response (VGPR), 6 patients (26%) achieved partial response (PR), and 5 patients (22%) achieved stable disease (SD). Progression-free survival (PFS) and Overall-survival (OS) were 4 and 11.9 months, respectively. There was no reported treatment-related mortality. The most common grade ≥3 adverse events were neutropenia (26%), thrombocytopenia (56.5%), and anemia (56.5%). CONCLUSIONS: KCd showed clinically meaningful efficacy and manageable safety profile in patients with triple-class RRMM in real-world.

Use of endpoints in multiple myeloma randomized controlled trials over the last 15 years: A systematic review.

Surrogate endpoints are being used more frequently in randomized controlled trials, even though they do not consistently corelate with patient outcomes. We systemically evaluated the use of surrogate endpoints in multiple myeloma randomized controlled trials over the past 15 years. We searched three databases (Pubmed, Embase, Cochrane) for multiple myeloma randomized controlled trials from January 1, 2005 to December 30, 2019. The primary outcome of our study was the proportion of randomized controlled trials that used overall survival as their primary endpoint. Secondary outcomes included the use of surrogate endpoints, and trends over time, and whether they differed based on study sponsorship. We included 151 randomized controlled trials in our analysis. The primary endpoint was overall survival (OS) in 17 (11.3%) of studies, progression free survival (PFS) or event-defined endpoints in 91 studies (60.3%) and response-based endpoints in 44 studies (29.1%). Quality of life was a primary endpoint in only three studies (2%). The use of OS as a primary endpoint decreased from 28.5% of trials from 2005 to 2009 to 5.5% from 2015 to 2019. There has been a decrease in the clinically meaningful endpoint of OS over the past 15 years in multiple myeloma randomized controlled trials. Use of quality of life as a primary endpoint remains exceedingly low. It remains paramount to recognize that the use of surrogate endpoints is imperfect, and care based upon them requires constant physician and patient re-analysis.

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study.

BACKGROUND: Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study. METHODS: DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with relapsed or refractory multiple myeloma with disease progression after three or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody with an Eastern Cooperative Oncology Group performance status of 0-2 were recruited, centrally randomly assigned (1:1) with permuted blocks (block size 4), and stratified by previous lines of therapy (≤4 vs >4) and cytogenetic features to receive 2·5 mg/kg or 3·4 mg/kg belantamab mafodotin via intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. The intention-to-treat population comprised all randomised patients, regardless of treatment administration. The safety population comprised all patients who received at least one dose of belantamab mafodotin. The primary outcome was the proportion of randomly assigned patients in the intention-to-treat population who achieved an overall response, as assessed by an independent review committee. This study is registered with ClinicalTrials.gov, NCT03525678, and is ongoing. FINDINGS: Between June 18, 2018, and Jan 2, 2019, 293 patients were screened and 196 were included in the intention-to-treat population (97 in the 2·5 mg/kg cohort and 99 in the 3·4 mg/kg cohort). As of June 21, 2019 (the primary analysis data cutoff date), 30 (31%; 97·5% CI 20·8-42·6) of 97 patients in the 2·5 mg/kg cohort and 34 (34%; 23·9-46·0) of 99 patients in the 3·4 mg/kg cohort achieved an overall response. The most common grade 3-4 adverse events in the safety population were keratopathy (in 26 [27%] of 95 patients in the 2·5 mg/kg cohort and 21 [21%] of 99 patients in the 3·4 mg/kg cohort), thrombocytopenia (19 [20%] and 33 [33%]), and anaemia (19 [20%] and 25 [25%]); 38 (40%) of 95 patients in the 2·5 mg/kg cohort and 47 (47%) of 99 in the 3·4 mg/kg cohort reported serious adverse events. Two deaths were potentially treatment related (one case of sepsis in the 2·5 mg/kg cohort and one case of haemophagocytic lymphohistiocytosis in the 3·4 mg/kg cohort). INTERPRETATION: Single-agent belantamab mafodotin shows anti-myeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma. FUNDING: GlaxoSmithKline.

Health Care Reimbursement, Service Utilization, and Outcomes among Medicare Beneficiaries with Multiple Myeloma Receiving Autologous Hematopoietic Cell Transplantation in Inpatient and Outpatient Settings.

Autologous hematopoietic stem cell transplantation (auto-HCT) is a complex procedure that can be performed in both inpatient (IP) and outpatient (OP) care settings. We examined reimbursement, service utilization, and patient financial responsibility among Medicare beneficiaries with multiple myeloma who underwent auto-HCT in the IP and OP settings using a merged dataset of the Center for International Blood and Marrow Transplant Research observational database and Centers for Medicare & Medicaid Services Medicare administrative claims data. Selection criteria included first auto-HCT, time from diagnosis to auto-HCT <18 months, and continuous enrollment in Medicare Parts A and B for 30 days before HCT index claims and 100 days post-HCT or until death. Total reimbursement and patient responsibility were adjusted for patient and disease characteristics using a weighted generalized linear model. The final cohort comprised 1640 patients, 1445 (88%) who received IP-HCT and 195 (12%) who received OP-HCT. The adjusted total mean reimbursement was higher for IP-HCT compared with OP-HCT ($82,368 [95% CI, $77,643 to $87,381] versus $46,824 [95% CI, $43,567-$50,325]; P < .0001). Adjusted total mean patient responsibility was $4736 for IP-HCT (95% CI, $4731 to $5133) and $6944 for OP-HCT (95% CI, $6296 to $7658) (P < .0001). Within 100 days post-HCT, 107 of the 195 OP-HCT recipients (55%) had at least 1 subsequent admission, compared with 348 of the 1445 IP-HCT recipients (24%). Reimbursement, service utilization, and financial responsibility varied by HCT setting. As the number of Medicare beneficiaries who undergo auto-HCT increases, coverage policy needs to consider how location of services leads to variations in the financial burden for both hospital systems and patients.

Antibiotic prophylaxis for patients with newly diagnosed multiple myeloma: Systematic review and meta-analysis.

OBJECTIVE: Ascertain the benefit of prophylactic antibiotics for patients with newly diagnosed multiple myeloma (MM), given that clinical trials evaluating this have had conflicting results. METHODS: We performed a systematic review and meta-analysis evaluating the use of prophylactic antibiotics in patients with MM and its impact on infection risk and mortality. RESULTS: Across three included studies, a total of 664 patients received antibiotics and 650 patients received no antibiotics. The overall incidence of infection within 3 months was lower for antibiotic group compared to placebo (18.4% vs 23.4%, RR: 0.79, 95% CI 0.62-1.00, P = .05, I2  = 6.5%). There was no difference in mortality in the first 3 months (1.5% vs 3.5%, RR: 0.47, 95% CI 0.17-1.27, P = .60, I2  = 28.1%). CONCLUSION: Antibiotic prophylaxis for a finite duration can decrease the overall incidence of infection within the first 3 months following diagnosis. This does not lead to a decrease in mortality. Further data on antibiotic resistance patterns, toxicity, healthcare expenditures, and the impact of antibiotics on subsequent therapies can assist providers in helping make decisions on prophylactic antibiotics with their patients.

Inpatient mortality of patients with multiple myeloma and renal impairment undergoing autologous stem cell transplantation.

OBJECTIVES: Further data are needed on the safety of high-dose melphalan and autologous stem cell transplant (HDM-ASCT) in patients with multiple myeloma (MM) and renal impairment. The objective of our study was to use the National Inpatient Sample (NIS) to determine inpatient mortality for patients with MM and renal impairment undergoing HDM-ASCT, as well as trends over time. METHODS: Using the NIS, we tracked hospital admissions for MM patients from 2002 to 2014 who underwent HDM-ASCT, using ICD 9 coding. RESULTS: The total weighted estimate of inpatient admissions for HDM-ASCT among MM patients was 47,253 from 2002 to 2014. A weighted total of 45 and 1709 patients with MM received peritoneal dialysis (PD) and hemodialysis (HD) during HDM-ASCT for MM, respectively. There was a markedly increased risk of inpatient mortality in patients on dialysis undergoing transplant (20.5% for PD patients, 13.8% for HD patients), even after accounting for other comorbidities (odds ratio of inpatient mortality of 6.193 [CI 3.585-10.701]). A significant decrease was noted in inpatient mortality for patients with ESRD undergoing HDM-ASCT over time from 15.6% in 2009 to 5% in 2014 (P < .001). CONCLUSION: Patients with MM on dialysis undergoing HDM-ASCT are at significantly increased risk of inpatient mortality.