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Simple Summary: Induction regimens using 4-drugs for patients with newly diagnosed multiple myeloma have shown impressive results in multiple trials. However, trials of 4-drug regimens typically use a 3-drug regimen as their comparator, which limits our ability to determine whether the benefit is from the specific combination of drugs or just the addition of more agents. We performed a meta-analysis to compare all trials that compared 4-drug to 3-drug regimens and found that the addition of an anti-CD38 antibody (daratumumab or isatuximab) resulted in improved responses, while 4-drug regimens without an anti-CD38 antibody performed similarly to 3-drug regimens. While the addition of an anti-CD38 antibody led to increased adverse effects, these were predominantly mild and easily managed. These data suggest that an anti-CD38 antibody should be part of all 4-drug induction regimens for newly diagnosed myeloma patients. The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients. [ABSTRACT FROM AUTHOR]

Background: Daratumumab's incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options. Objective: This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara. Methods: Thirty-one patients with AL were included in this bi-institutional retrospective analysis. Results: Dara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections. Conclusion: These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure. [ABSTRACT FROM AUTHOR]

This retrospective cohort study used Taussig Cancer Center's Myeloma Patient Registry to identify adults with multiple myeloma diagnosed between January 2017-December 2021. Electronic health records data captured time from diagnosis to initial prescription fill for oral antimyeloma medications and initiation of facility administered or oral antimyeloma treatment. We identified 720 patients with a mean age at diagnosis of 67 years ±11; 55% were male, 77% White, 22% Black, 1% other races, covered by private insurance (36%), traditional Medicare (29%), Medicare Advantage (25%), and Medicaid (8.3%). Over a third of patients (37%) resided in an area in the most disadvantaged area deprivation index (ADI) quartile. The median available follow-up was 765 days. Seventy-five percent of the cohort filled an oral antimyeloma medication prescription (excluding corticosteroids), with a median time to fill of 28 days (IQR, 15–61). In the multivariable Cox regression model, Black race (vs. White, adjusted hazard ratio [aHR], 0.61, 95% CI, 0.42–0.87), older age at diagnosis (aHR per 1 year, 0.97, 95% CI, 0.95–0.98), diagnosis during an inpatient admission (aHR, 0.63, 95% CI, 0.43–0.92), and estimated glomerular filtration rate ≤29 ml/min/1.73 m2 (vs. ≥60, aHR, 0.46, 95% CI, 0.29–0.73) were negatively associated with prescription fill for oral antimyeloma medication at 30 days, while insurance type and ADI were not significant predictors. [ABSTRACT FROM AUTHOR]

Introduction: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. Results: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. Conclusion: Among bacteremic AML patients in the post‐HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low. [ABSTRACT FROM AUTHOR]

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell‐directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi‐institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3 months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6 months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6 months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p = 0.006), and achievement of ≥VGPR (OR 21.7 p < 0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p = 0.09). With a median follow‐up of 36.4 months, the median overall survival (OS) was 11 months. On multivariable analysis, achievement of renal response (hazard ratio [HR] 0.3, p < 0.0001) and newly diagnosed disease (NDMM; HR 0.43, p = 0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab‐based regimens had a trend for better OS (p = 0.15), compared to other regimens, but the difference was not significant. At the end of follow‐up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab‐based therapies showing promise. [ABSTRACT FROM AUTHOR]

The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion. [ABSTRACT FROM AUTHOR]

PURPOSE Little is known about the role of social determinants of health (SDOH) in the utilization of novel treatments among patients with newly diagnosed multiple myeloma (NDMM). METHODS This retrospective cohort study used Taussig Cancer Center's Myeloma Patient Registry to identify adults with NDMM between January 1, 2017, and December 31, 2021. Electronic health records data captured treatment with (1) triplet or quadruplet regimen and (2) lenalidomide during the first year after NDMM, and (3) stem-cell transplant (SCT) through December 31, 2022. Multivariable logistic regression models examined associations of demographic/clinical characteristics and SDOH with care patterns. RESULTS We identified 569 patients with median age at diagnosis of 66 years (IQR, 59-73); 55% were male, 76% White, 23% Black, 1.1% other races, insured by Medicare (51%), private payer (38%), Medicaid (8.3%), and self-pay/other (1.8%). In the multivariable models, self-pay/other payers (adjusted odds ratio [AOR], 0.15 [95% CI, 0.03 to 0.54]) was associated with lower odds of triplet or quadruplet regimen, compared with Medicare. Private insurance (AOR, 0.48 [95% CI, 0.27 to 0.86]) and self-pay/other payers (AOR, 0.16 [95% CI, 0.04 to 0.74]) had lower odds of lenalidomide. Black patients (v White; AOR, 0.47 [95% CI, 0.26 to 0.85]) and patients treated at regional hospitals (v Taussig Cancer Center; AOR, 0.27 [95% CI, 0.12 to 0.57]) had lower odds of SCT. The odds of receiving triplet or quadruplet regimen, lenalidomide, and SCT also varied by the year of NDMM. CONCLUSION Care for NDMM varied based on race, insurance type, year of diagnosis, and treatment facility. It may be useful to examine the impact of insurance-related characteristics and recent policy initiatives on care disparities. [ABSTRACT FROM AUTHOR]

This article validates the use of the GATMO score in predicting non-relapse mortality (NRM) in multiple myeloma (MM) patients after autologous hematopoietic cell transplant (AHCT). The study included 513 MM patients who underwent AHCT, and the GATMO score reliably stratified the patients' risk of NRM. The score was found to be useful in identifying patients at higher risk of NRM, although its ability to predict overall survival (OS) was modest. The authors suggest that the GATMO score may be a useful tool for evaluating MM patients being considered for AHCT, but further prospective validation is needed. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. This analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2023, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, objective response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care.