Levine Cancer Institute

Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ doublet maintenance with bortezomib plus lenalidomide (VR). We evaluated outcomes with VR versus lenalidomide alone (R) in HRMM. Methods: We conducted a multicenter retrospective study through the US Myeloma Innovations Research Collaborative (USMIRC), including adults with HRMM who received R or VR maintenance following ASCT between January 2009 and January 2024. HRMM was defined by del(17p), t(4;14), t(14;16), or t(14;20), with or without 1q gain. PFS and OS were estimated using Kaplan-Meier methods. Median follow-up was 91 months. Baseline characteristics, induction regimens, and post-transplant response depth were well balanced between the groups. Median PFS was 51 months (95% CI, 20-NR) with VR and 36 months (95% CI, 31-56) with R (p > 0.05). Median OS was 103 months (95% CI, 90-NR) and 110 months (95% CI, 94-NR), respectively (p > 0.05). VR was associated with numerically longer PFS, although the difference was not statistically significant. No treatment-related mortality occurred within 100 days post-ASCT. Conclusions: In this multicenter real-world analysis of HRMM, VR maintenance did not result in statistically significant improvements in PFS or OS compared with lenalidomide alone. These findings underscore the need for prospective, risk-adapted trials incorporating novel maintenance strategies, including CD38- and BCMA-directed therapies, in high-risk disease.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells and a rapidly evolving treatment landscape. Bispecific antibodies targeting B-cell maturation antigens (BCMA) have emerged as promising therapeutic options for relapsed and/or refractory multiple myeloma (RRMM). This retrospective study evaluated the efficacy and safety of teclistamab, a BCMA-directed bispecific antibody, in patients with RRMM with renal impairment (RI) at baseline compared to those without. Conducted across seven academic centers, the study included 195 patients with RRMM, of whom 34 had baseline RI. Performance status, previous lines of treatment, and prior BCMA exposure were identified as significant predictors of progression-free survival. Notably, patients with RI demonstrated overall response rates and toxicity profiles comparable to those without RI, although they required more packed red blood cell transfusions. No statistically significant differences were observed in adverse events, including cytokine release syndrome and infections. Overall, the findings support the efficacy and safety of teclistamab in patients with RRMM and RI, highlighting the need for prospective clinical trials to optimize the treatment strategies for this population.

The pivotal clinical trials, CARTITUDE-1 and KarMMa-3, showed promising response rates in relapsed and refractory multiple myeloma (RRMM) with use of BCMA-directed CAR T-cell therapy; however, a major challenge is determining suitability in patients who do not meet trial inclusion criteria due to suboptimal organ function. In this multicenter retrospective study, we evaluated the safety and efficacy of BCMA CAR-T therapy in patients with RRMM and renal impairment (RI), defined as creatinine clearance (CrCL) of less than 45 mL/min. We evaluated 223 patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) between May 2021 and April 2024. Outcomes were compared between baseline RI (11.2%) and normal renal function (nRF) cohorts. Response rates were similar at 1 month (p = 0.09), 3 months (p > 0.9), and 6 months (p = 0.8). Progression-free survival (PFS) was 21.9 months in the RI group compared to 15 months in the nRF group (p = 0.32), while overall survival (OS) was 27.9 months for patients with nRF versus not reached for patients with RI (p = 0.87). Patients with RI had higher rates of immune effector cell-associated neurotoxicity syndrome (ICANS) (60% vs. 19%, p = 0.04) and infections (44% vs. 20%, p = 0.008). We found that BCMA CAR-T demonstrated comparable efficacy in RRMM patients with baseline RI, although these patients exhibited increased rates of neurotoxicity and infections.

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP). Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety. Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs. Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.

Purpose: This study describes the design and implementation of a multimodal prehabilitation program for patients undergoing radical cystectomy, utilizing the comprehensive geriatric assessment (CGA) to identify and address preoperative impairments. It also characterizes baseline patient findings obtained through the CGA.Materials and Methods: We describe a multimodal prehabilitation program within the Department of Supportive Oncology at Atrium Health Levine Cancer, a large academic hybrid cancer center in United States. Patients with bladder cancer scheduled for radical cystectomy were referred by the genitourinary oncology team at least 2 weeks before surgery and underwent baseline evaluation using the CGA. Tailored interventions were subsequently implemented to address vulnerabilities identified during the assessment.Results: Between February 2022 and January 2024, 142 patients undergoing cystectomy were offered prehabilitation; 54 (38%) enrolled, and an additional 4 completed the program before its formal launch. Assessments were performed either in person or virtually. At baseline, 64% of participants were classified as intermediate frail or frail; 40% screened positive for cognitive impairment, and 57% were either malnourished or at risk of malnutrition. All patients received individualized exercise prescriptions based on their frailty phenotype (fit, intermediate frail, or frail). Referrals were made to an exercise specialist, registered dietitian, or counselor, depending on identified needs.Conclusion: The use of the CGA facilitated the implementation of a multimodal prehabilitation program for patients undergoing radical cystectomy. High rates of preoperative frailty, cognitive impairment, and nutritional risk were observed, allowing targeted interventions before surgery. While the program demonstrated successful integration and participation, future efforts should focus on standardizing intervention delivery and adherence monitoring to assess the objective impact of prehabilitation on postoperative outcomes.