7510 Background: Tec, a B-cell maturation antigen x CD3 bispecific antibody (bsAb), and Tal, a G protein-coupled receptor class C group 5 member D x CD3 bsAb, are approved for the treatment of pts with triple-class exposed (TCE) RRMM. Cytokine release syndrome (CRS) is a common adverse event associated with T-cell therapies. CRS occurred in 72% and 73-79% of pts in the MajesTEC-1 (TEC-1) and MonumenTAL-1 (TAL-1) studies, respectively. One cohort of pts in TEC-1 received prophyToci, resulting in a lower rate of CRS (26%) without negatively impacting safety or efficacy. A cohort of pts in TAL-1 received prophyToci, with 18% experiencing CRS; safety and efficacy were comparable to the overall TAL-1 population. Methods: This nonrandomized, multicenter, prospective study evaluates prophyToci in RRMM pts treated with Tec (Arm A) or Tal (Arm B) using the approved step-up dose (SUD) schedule in the OP setting. ProphyToci 8 mg/kg was administered before SUD 1 of either Tec or Tal. Specific recommendations (home monitoring, IV immunoglobulin [IVIG] for IgG levels <400 mg/dL) and restrictions (caregiver requirements and travel distance) are also provided for pt safety. Primary endpoint is incidence of any grade CRS in cycles 1-2. Secondary endpoints include safety and efficacy measures. Safety parameters encompass incidence of Grade ≥2 CRS, any grade recurrent CRS, any grade infections, neurotoxicity (NT), and neutropenia throughout the study. Efficacy endpoints include overall response rate (ORR), best overall response (BOR) and progression-free survival (PFS). Results: As of 06 January 2026, 43 pts enrolled in Arm A, and 7, in Arm B. In Arm A, the CRS rate was 5%, all G1. In Arm B, G1 CRS occurred in 14% of pts. Adverse events G≥3 included neutropenia (G3, n=4; G4, n=6), anemia (G3, n=1), and febrile neutropenia (G3, n=1). Twenty pts (47%) in Arm A experienced infections, with 19% ≥G3. Among Arm A patients who experienced infections, 10 (50%) exhibited IgG levels <400 mg/dL, of whom 2 (20%) received IVIG. In Arm B, 4 pts (57%) experienced infections, with 29% (n=2) ≥G3. BOR in Arm A included 3 stringent complete responses (sCRs), 6 CRs, 11 very good partial responses (VGPR), 8 PRs, 1 stable disease, 5 progressive disease (PD), and 9 non-evaluable pts. Among the 34 evaluable pts in Arm A, the ORR was 82%. BOR in Arm B included 1 sCR and 6 non-evaluable pts. After a median follow-up of 11.8 months, 74.4% of pts (n=32) in Arm A did not experience progression. Conclusions: A single dose of prophyToci before SUD 1 of Tec or Tal reduced the incidence of CRS, with no impact on safety or efficacy, and supports administration of these bsAbs in the OP setting. The protocol was amended to add an arm evaluating the effect of prophylactic oral dexamethasone on CRS in pts treated with Tec (Arm C). Enrollment is ongoing (NCT05972135). Clinical trial information: NCT05972135 .

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment. Materials and methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed. Results: This analysis included: PREAMBLE n = 215; Connect MM n = 232; Flatiron Health n = 845. Median age at index was 69.0 years, median 3 prior lines of therapy; > 50% male. The most common index regimens accounted < 15% of treatments (most common PREAMBLE, Connect MM: carfilzomib +/- dexamethasone; Flatiron Health: pomalidomide+daratumumab+dexamethasone); most patients received classes that they had previously; >= 93% were triple-class exposed (immunomodulatory drug, proteasome inhibitor, anti-CD38 mAb). In PREAMBLE, Connect MM and Flatiron Health, respectively: 80.9%, 68.1% and 77.2% were lenalidomide- and anti-CD38 mAb-refractory; 69.3%, 67.2% and 71.1% were triple-class refractory (TCR); median PFS: 5.2 (95% CI 3.7-6.7), 4.4 (3.5-5.6) and 5.3 months (4.8-6.0); median OS: 19.3 (15.8-26.1), 14.2 (11.0-16.9) and 23.1 months (19.0-28.6). PFS and OS were shorter in lenalidomide- and anti-CD38 mAb-refractory patients versus those who were not refractory to both. A similar pattern was observed for TCR patients versus non-TCR patients. Conclusion: There is no uniform standard of care for patients with RRMM with prior exposure to lenalidomide and anti-CD38 mAbs. Survival outcomes are poor, with a need for effective treatments for these patients.

Patient characteristics, treatment patterns, quality of life, and survival were analyzed among long-surviving patients of multiple myeloma from the Connect (R) MM Registry. Long survivors were generally younger and healthier at diagnosis when compared with non-long survivors. The results provided insights beyond the long-term follow-up of clinical trials, indicating the importance of real-world longitudinal follow-up. Background: Over the last 15 years, improvements in patient management and treatments have been associated with longer survival in patients with multiple myeloma (MM). The Connect MM Registry is a long-running, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM (NDMM). We assessed the demographics, clinical characteristics, and treatment patterns of long-term survivors (LTS) enrolled in this registry. Methods: Adults with NDMM (n = 3,011) were enrolled from 250 community, academic, and government sites across the US from 2009-2016. Baseline characteristics, treatment patterns, quality of life (QoL), and overall survival (OS) were examined among LTS, defined as patients with follow-up of >= 8 years after enrollment. Results: As of February 7, 2023, 518 patients were LTS and 2,493 were non-LTS. LTS were generally younger and had better performance status at enrollment compared with non-LTS. Most (65%) LTS received stem cell transplants and few (2%) experienced disease progression within 6 months of starting first line of therapy. At data cutoff, 63% of LTS were still on treatment at their most recent visit. QoL scores and QoL questionnaire completion rates were consistently higher among LTS than non-LTS. The estimated 8-year OS rate of all patients enrolled in the registry was 40%, comparable to an observed 8-year survival of 39% from the Surveillance, Epidemiology, and End Results (SEER) database. Conclusion: This analysis provides insights on long-surviving patients with MM using real-world data and therefore presents generalizability beyond data obtained in long-term follow-up of clinical trials, underscoring the need for longitudinal follow-up through registries.

Aim: To compare the effectiveness of in-class transition to all-oral ixazomib-lenalidomide-dexamethasone (IRd) following parenteral bortezomib (V)-based induction versus continued V-based therapy in US oncology clinics. Patients & methods: Non-transplant eligible patients with newly diagnosed multiple myeloma (MM) receiving in-class transition to IRd (N = 100; US MM-6), or V-based therapy (N = 111; INSIGHT MM). Results: Following inverse probability of treatment weighting, overall response rate was 73.2% with IRd versus 57.5% with V-based therapy (p < 0.0001). Median duration of treatment was 10.8 versus 5.3 months (p < 0.0001). Overall, 18/24% of patients discontinued IRd/V-based therapy due to adverse events. Conclusion: IRd after V-based induction was associated with significantly improved overall response rate and duration of treatment than continued V-based combination therapy. Clinical Trial Registration: US MM-6: NCT03173092; INSIGHT MM: NCT02761187 (ClinicalTrials.gov).

Background: Teclistamab is the only approved BCMA×CD3 bispecific antibody with a personalized, weight-based dosing schedule for the treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM). It is FDA approved for patients (pts) of therapy (LOTs), including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. In the pivotal MajesTEC-1 study (Moreau et al NEJM 2022), teclistamab showed deep and durable responses and a manageable safety profile in heavily pretreated pts with RRMM who had limited treatment options. The incidence of all grade cytokine release syndrome (CRS) during the first 2 cycles was 70%. Most pts experienced CRS following step-up doses 1 (42%) or 2 (35%), or the initial treatment dose (24%); 33% of pts experienced recurrent CRS. Most CRS events were grade 1/2 and fully resolved without discontinuation or dose reduction of teclistamab. One (0.6%) case of grade 3 CRS occurred in a pt who pneumonia but resolved in 2 days. No grade 4 or 5 CRS occurred. Tocilizumab is a monoclonal antibody targeting the interleukin-6 receptor (IL-6R) which is used to manage CRS resulting from T-cell redirection therapy. Preclinical data indicate that inhibition of IL-6 signaling prior to teclistamab administration can prevent CRS development without impacting anti-tumor activity (Li et al Ann. Oncol. 2019). In MajesTEC-1, pts who received a single IV dose of tocilizumab before the first teclistamab step-up dose (n=23) showed a reduction in the incidence of all grades of CRS, compared with the overall study population (26% vs 72%). Currently, there are no data on the safety of administering the step-up doses of teclistamab in the outpatient (OP) setting, but OP step-up dosing may make teclistamab more accessible. Therefore, we seek to investigate whether the use of prophylactic tocilizumab can reduce the incidence and severity of CRS associated with teclistamab and allow safe OP administration of the step-up dosing. Methods: This single-arm, non-randomized, multicenter, prospective study (NCT05972135) will evaluate CRS incidence and severity after prophylactic tocilizumab in pts treated with teclistamab in the OP setting. A target of 50 participants will be enrolled with an initial PK/PD safety cohort (n=10). Objectives through end of study include recurrent CRS, grade ≥3 and any grade infections, neurotoxicity including ICANS, neutropenia, febrile neutropenia, and efficacy. Eligible pts are ≥18 years with a documented diagnosis of RRMM who have previously received ≥4 LOTs. Pts with rapidly progressing disease, central nervous system involvement, active infection, or contraindication to tocilizumab will be excluded from the trial. Prior to the treatment phase, pts will participate in a 28-day screening phase to determine study eligibility. During the treatment phase, a single dose of tocilizumab will be administered at 8 mg/kg IV, 2 to 4 hours prior to step-up dose 1 of teclistamab (Cycle 1 Day 1) in an outpatient setting (Figure 1). Teclistamab will then be administered at step-up doses of 0.06 mg/kg subcutaneously (SC) (Cycle 1 Day 1) and 0.3 mg/kg SC (Cycle 1 Days 3-5), followed by 1.5 mg/kg SC (Cycle 1 Day 8), with weekly administration for twelve 28-day cycles or until disease progression or unacceptable toxicity. Teclistamab may be reduced to 1.5 mg/kg SC every two weeks for participants who achieve partial response or better after 6 months of therapy. Safety evaluations will include physical examination, vital sign measurements, neurological examination, assessment of ECOG performance status, and clinical safety laboratory assessments. IVIG is recommended in pts with serum IgG <4 g/L. Follow-up of participants during the study will include monitoring for all adverse events, disease progression, and survival until end of study. By studying the feasibility and safety of administering the step-up dosing schedule in an outpatient setting, teclistamab may become more accessible to pts with RRMM and limited treatment options.

Patients with multiple myeloma (MM) are initially treated with triplet or quadruplet combination regimens that include proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. However, most patients with MM experience progression after initial treatment and need efficacious subsequent-line combinations that incorporate new drug classes. Multiple studies in this relapsed/refractory MM population have shown progression-free survival (PFS) benefit; however, it is important that this translates into overall survival (OS) benefit for patients, as OS considers both efficacy and safety. Currently, daratumumab-containing regimens are widely used in this setting because triplet daratumumab combinations have shown significant PFS and OS benefits compared with their respective doublet backbones without daratumumab. Belantamab mafodotin, a B-cell maturation antigen-targeting antibody-drug conjugate, has demonstrated single-agent sustained maintenance of deep and durable response with longer follow-up, owing to its multimodal mechanism of action that includes monomethyl auristatin F-induced cytotoxic cell death, antibody-dependent cellular cytotoxicity/phagocytosis, and immunogenic cell death. This has led to improvement in long-term clinical outcomes, including duration of response (DOR). Therefore, we anticipate that belantamab mafodotin in combination with standard-of-care therapies will show increasing OS benefit with longer follow-up. DREAMM-7 (NCT04246047) is a global, 1:1 randomized, open-label, phase 3, head-to-head trial comparing the efficacy and safety of 2 triplets-belantamab mafodotin, bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd)-in patients with progression of MM after ≥1 prior line of therapy. The primary endpoint was independent review committee-assessed PFS. Secondary endpoints included OS, DOR, minimal residual disease (MRD) negativity, and time from randomization to disease progression after subsequent antimyeloma therapy or death from any cause (PFS2) (Hungria et al. N Engl J Med 2024). In total, 494 patients were randomly assigned to receive BVd (n=243) or DVd (n=251). Baseline characteristics were balanced; overall, 51% of patients had received 1 previous line of therapy, 52% had exposure to lenalidomide, 34% had disease that was refractory to lenalidomide, and 28% had high-risk cytogenetic abnormalities. At a median follow-up of 28.2 months (range, 0.1-40.0 months), the primary endpoint was met, with a median PFS (95% CI) of 36.6 months (28.4 months-not reached [NR]) with BVd and 13.4 months (11.1-17.5 months) with DVd (hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P<.00001). BVd was associated with higher rates of complete response or better plus MRD negativity (25% vs 10%) and a more favorable restricted mean DOR (P<.001) than DVd. The median DOR (95% CI) was 35.6 months (30.5 months-NR) with BVd and 17.8 months (13.8-23.6 months) with DVd. Treatment benefits with BVd were also maintained after subsequent antimyeloma therapy, with an HR (95% CI) for median PFS2 of 0.56 (0.41-0.76). OS rates at 18 months with BVd vs DVd was 84% vs 73%, respectively. While median OS was NR in either arm at this first interim analysis, there was a strong trend in favor of BVd vs DVd, with an HR of 0.57 (95% CI, 0.40-0.80). Of note, in the CASTOR trial, median OS with DVd was 49.6 months in patients with a median of 2 prior lines of therapy. We will present the results from the second planned interim analysis of DREAMM-7, with an approximate 3.3 years of follow-up; this will provide further insight on the potential survival benefit with BVd and include updates on response depth, DOR, MRD-negativity rates, and PFS2. Overall, the DREAMM-7 head-to-head study of BVd vs DVd demonstrated statistically significant PFS benefit with BVd in patients with relapsed/refractory MM who have received ≥1 prior line of therapy. BVd also led to a deeper response and longer DOR than DVd. Since a strong and clinically meaningful early OS benefit with BVd was observed, updated practice-changing OS results are anticipated and will be presented at ASH 2024. Taken together, these results support BVd as a potential new standard of care in MM at first relapse or later. Funding: GSK (Study # 207503) Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Background: Long-term proteasome inhibitor (PI)-based therapy can improve overall survival and delay disease progression for patients (pts) with multiple myeloma (MM), but this can be particularly difficult to achieve in pts with comorbidities. US MM-6 is a prospective, community-based phase 4 study of in-class transition (iCT) from parenteral bortezomib (V)-based induction to all-oral ixazomib-lenalidomide-dexamethasone (IRd) in pts with newly diagnosed MM (NDMM; NCT03173092). US MM-6 aims to extend the duration of PI-based therapy and improve clinical outcomes while maintaining pt quality of life (QoL). We report results by number of treatment cycles received. Methods: Transplant-ineligible/delayed-transplant (≥24 months) pts with NDMM, who had achieved a response of stable disease or better after 3 cycles of V-based induction, were enrolled at US community sites to receive IRd for up to 39 cycles or until progression or toxicity. For this analysis, data were assessed in subgroups of pts who had received 1−3, 4−9, and >9 IRd cycles (or 4-6, 7-12, and >12 cycles of overall PI-based therapy, respectively). Comorbidities were assessed via a modified Charlson Comorbidity Index (mCCI); a score of 0 indicates no comorbidities, while higher scores indicate higher probability of mortality in pts with comorbidities (Charlson, J Chronic Dis 1987). Results: At data cutoff (October 12, 2023), 140 pts had been enrolled and treated, 27 (19%) pts had received 1−3 IRd cycles, 35 (25%) had received 4−9 cycles, and 78 (56%) had received >9 cycles. Most common reasons (>25%) for treatment discontinuation were pt withdrawal (41%) and treatment-emergent adverse events (TEAEs, 37%) in the 1−3 cycles group; TEAEs, progressive disease, or physician decision (26% each) in the 4−9 cycles group; and AEs (31%) in the >9 cycles group. In the 1−3, 4−9, and >9 cycles groups, respectively, median age was 75, 73, and 71 yrs, and 52%, 46%, and 37% were aged ≥75 yrs; 59, 74, and 50% of pts were male; and 26, 20, and 38% had a baseline International Staging System score of III. Of the pts in the 1−3, 4−9, and >9 cycles groups, 89, 91, and 97% had ≥1 comorbidity at baseline, respectively, including renal/urinary disorders (41, 34, and 29%), cardiac disorders (30, 20, and 32%), peripheral neuropathy (PN) or sensory PN (30, 9, and 23%), and diabetes mellitus (19, 11, and 22%); 48, 49, and 46% had an mCCI score of 0, and 52, 51, and 54% had an mCCI score of 1-5. In pts who received 1−3, 4−9, and >9 IRd cycles, median PFS in months was 7.5 (95% confidence interval [CI] 2.7-not reached [NR]), 24.6 (5.8-NR), and NR (NR-NR); the 2-year PFS rates were 30% (95% CI 7−59), 51% (31−68) and 81% (69−88), respectively. Grade ≥3 TEAEs were reported in 59% of pts in the 1−3 cycles group, 60% in the 4−9 cycles group, and 78% in the >9 cycles group; grade ≥3 TEAEs were treatment-related in 30, 37, and 40% of pts, respectively. Serious TEAEs were reported in 48% of pts in the 1−3 cycles group, 34% in the 4−9 cycles group, and 47% in the >9 cycles group; serious TEAEs were treatment-related in 19, 9, and 13% of pts, and 2, 1, and 2 pts died on-study, respectively. Any grade TEAEs reported in ≥25% of pts were diarrhea (26%) in the 1−3 cycles group; PN not elsewhere classified (NEC; 34%), fatigue (34%), diarrhea (34%), and edema NEC (26%) in the 4−9 cycles group; and diarrhea (68%), PN NEC (53%), fatigue (42%), edema NEC (38%), arthralgia (35%), nausea (33%), and back pain (29%) in the >9 cycles group. Grade ≥3 TEAEs reported in ≥5% of pts overall were diarrhea (9%), decreased neutrophil count (6%), pneumonia (6%), anemia (5%), and decreased platelet count (5%). Conclusions: In non-transplant pts with NDMM, iCT from V-based induction to all-oral IRd permits long-term PI-based treatment while maintaining a tolerable safety profile. Despite the high percentage of pts with comorbidities, represented by mCCI scores of ≥1 across all cycle groups analyzed, the majority of pts received >9 IRd cycles (or >12 cycles of PI-based therapy) with no new safety concerns reported, demonstrating feasibility for longer treatment duration. As previously reported, long IRd treatment leads to clinically meaningful benefits in patients with NDMM (Facon, Blood 2021). Long-term triplet consolidation with IRd may delay progression and provide an alternative and convenient approach to induction/maintenance for community-based NDMM pts who are not eligible for upfront transplantation, including in pts with comorbidities.

PURPOSE:Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited.METHODS AND MATERIALS:The Connect® MM Registry is a large, US multicenter, prospective observational cohort study of adult patients with newly diagnosed MM from mostly community sites. RT utilization and outcomes were analyzed quarterly throughout treatment. Factors associated with RT use were identified via multivariable analysis.RESULTS:A total of 3011 patients were enrolled in the Connect MM Registry with 903 patients (30%) having received RT at any time. There was a significant difference (P < .05) in overall RT use among patients with an Eastern Cooperative Oncology Group performance status of 0 to 1 versus ≥2, International Staging System disease stage I/II versus III, a history of plasmacytoma or a novel agent in their first regimen, and any number of bone lesions or severe osteoporosis/fracture. RT use was associated with having bone lesions or severe osteoporosis (vs not having bone lesions). Additionally, RT use was associated with ethnicity (Hispanic vs not) and Connect MM Registry cohort (cohort 1 [enrolled 2009-2011] vs 2 [enrolled 2012-2016]). In the 6 months before death, increased RT use was associated with increasing number of treatment lines (P < .0001) and high- versus standard-risk disease (per International Myeloma Working Group criteria; P = .0028).CONCLUSIONS:Real-world results from the Connect MM Registry show RT is frequently used and is associated with clinical factors, including performance status and disease stage. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms or delay systemic therapy. Toward the end of life, RT is more frequently used for palliation when treatment options are often limited.

Characteristics and long-term outcomes for nontransplanted patients receiving frontline treatments for multiple myeloma are not well understood. Results from the Connect (R) MM Registry indicate that the common triplet regimen, lenalidomide, bortezomib, and dexamethasone (RVd), is active across age groups and provide realworld data to better understand outcomes with RVd in patients with newly diagnosed multiple myeloma. Background: Lenalidomide (R), bortezomib (V), and dexamethasone (d) is a standard-of-care regimen in newly diagnosed multiple myeloma (NDMM); however, characteristics and outcomes for nontransplanted patients receiving frontline RVd are not well understood. Patients: The Connect (R) MM Registry is a large, US, multicenter, prospective observational cohort study of NDMM patients. Methods: This analysis investigated characteristics and outcomes of patients who received RVd alone or followed by Rd or R (RVd +/- Rd/R) who did not undergo frontline autologous stem cell transplantation. Results: As of August 2021, 314 of 1979 nontransplanted patients received RVd +/- Rd/R as initial therapy. Of these, 135 were aged <= 65 years and 179 were > 65 years. 108 patients had time to relapse (TTR) of <= 12 months and 182 had TTR > 12 months. Baseline characteristics were comparable regardless of TTR and age group except renal function, which was more commonly impaired in older patients. Among patients aged <= 65 and > 65 years, median duration of first-line treatment was 6.3 and 9.0 months, median time to next line for those who received second-line therapy was 15.5 and 15.2 months, median progression-free survival (PFS) was 19.3 and 23.0 months, and median overall survival was 60.0 and 59.1 months, respectively. High-risk disease (per IMWG criteria) and high serum calcium were associated with higher hazard of progression or death; the adjusted PFS hazard ratio with respect to age (<= 65 vs. > 65 years) based on multivariable analysis was 1.18 (0.89-1.57; P = .25). Conclusion: These results indicate RVd is active across age groups and provide a better understanding of outcomes with RVd in NDMM.

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028.

We analyzed vaccination rates and associated outcomes of patients with multiple myelom in the INSIGHT MM study. Influenza vaccination in the prior 2 years and pneumococcal vaccination in the prior 5 years impacted overall survival versus no vaccination. Additionally, deaths due to infections were lower among vaccinated versus non-vaccinated patients. Vaccination status should be recorded in prospective clinical trials as it may affect survival. Background: Infections are a common reason for hospitalization and death in multiple myeloma (MM). Although pneumococcal vaccination (PV) and influenza vaccination (FV) are recommended for MM patients, data on vacci-nation status and outcomes are limited in MM. Materials and Methods: We utilized data from the global, prospective, observational INSIGHT MM study to analyze FV and PV rates and associated outcomes of patients with MM enrolled 2016-2019. Results: Of the 4307 patients enrolled, 2543 and 2500 had study-entry data on FV and PV status. Overall

What is this summary about? The aim of this plain language review article is to help you to understand biosimilar medicines (called biosimilars) by giving a summary of biologic medicines and biosimilars. It is based on the experience of an international panel of physicians with expertise on biosimilars who discussed and agreed on the topics and information included in this review article. Biologic medicines are medicines that come from living organisms such as bacteria and animal or plant cells. Biosimilars are a group of approved biologic medicines that are similar to original biologic medicines that are already available. This review explains how biosimilars are developed and approved, and how they are used to treat people with cancer. It also answers some common important questions people with cancer might have when taking biosimilars.The purpose of this plain language review is to help you to understand the findings from recent research. This review reports information from peer-reviewed literature and other sources available in the public domain (e.g., regulatory documents or product information labels). The findings may differ from those of other review articles. Health professionals should make treatment decisions based on all available evidence.

Introduction: Despite the development of advanced treatment options, multiple myeloma (MM) remains an incurable disease. Most MM patients ultimately relapse and require further treatments. MM patients who are triple class exposed (TCE) to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies have particularly poor outcomes and reduced probability to transition to a next therapy option. In the past few years, several novel therapies including Chimeric Antigen Receptor T-cell (CAR-T) therapies and bispecific antibody therapies became available for TCE patients in the later line setting. Using latest data, this study aims to characterize MM patients treated in US Oncology Network, who were TCE with at least 4 prior lines of therapy (4+ prior LOTs), and to describe their characteristics, treatment patterns, and clinical outcomes. Because treatment history such as penta-drug exposure status (at least two PIs, at least two IMiDs, and at least one anti-CD38) and patient characteristics such as race (White and African American) are known to impact disease outcomes, the impact of these subgroups on treatment to discontinuation or death (TTD) and time to next treatment or death (TTNT) were also evaluated. Methods: Patients with MM who were TCE with 4+ prior LOTs were identified retrospectively from the iKnowMed (iKM) oncology EMR database of the US Oncology Network. Those eligible initiated the next line of therapy (index date) from July 3, 2019 (when additional new treatment options became available) through April 3, 2023, and were followed to the earliest of death, last activity, or end of the study period. Clinical outcomes including TTD and TTNT were analyzed and estimated using the Kaplan-Meier method. Results: A total of 561 TCE patients with 4+ prior LOTs were included in the study, including 95 (16.9%) African American, 387 (69.0%) White, and 310 (55.3%) patients who were penta-drug exposed before index. Key demographic and clinical characteristics are listed in Table 1. The mean (SD) number of prior lines of therapy for the overall TCE & 4+ prior LOTs MM patients before index date was 4.6 (1.2). Prior to the index date, most patients were exposed to daratumumab (99.8%), lenalidomide (95.4%), bortezomib (93.2%), pomalidomide (77.7%), and carfilzomib (61.9%). Excluding corticosteroids, the most common index treatments were pomalidomide- (34.4%), daratumumab- (32.2%), and carfilzomib- (29.1%) based regimens. The most frequently used therapy were triplets (55.1%), followed by doublets (29.3%) and quadruplets (11.9%). CAR-T therapies were not captured in the data, and only 3 patients received bispecific antibody therapy. The estimated median (95% CI) TTD and TTNT in months for the overall TCE with 4+ prior LOTs MM patients were 4.2 (3.9, 5.1) and 6.5 (5.5, 7.4), respectively. TTD and TTNT estimates for the three subgroups are listed in Table 2. Conclusions: This study demonstrates there are limited effective treatment options for heavily treated MM patients in the US Oncology Network. Novel therapies have not been widely used. Clinical outcomes in these patients remain poor, as demonstrated by the short TTD and TTNT. More than half of the patients in the study were penta-drug exposed, a subgroup that showed even worse clinical outcomes than the overall patient group. Racial disparity was also observed, with African American patients appearing to have shorter TTD and TTNT than White patients. The findings highlight the continued need for effective treatments for heavily treated MM patients, including those with demonstrated particularly poor outcomes. Studies investigating innovative therapies to improve the outcomes for these patients are in process.