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8036 Background: Teclistamab is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in MajesTEC-1 (NCT04557098), an open-label, single-arm, phase 1/2 trial in patients with RRMM who had received ≥3 prior lines of therapy (LOT) and were TCE to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Given the absence of a control arm in MajesTEC-1, we assessed the comparative effectiveness of teclistamab versus treatment regimens using an external control arm from a real-world database. Methods: An external control arm for MajesTEC-1 was created from eligible patients in the nationwide de-identified electronic health record-derived Flatiron Health multiple myeloma cohort database who started a new line of therapy (physician’s choice) following triple-class exposure between January 2011 and August 2021, received ≥3 prior LOT, and satisfied key MajesTEC-1 eligibility criteria. Individual patient data from MajesTEC-1 included patients who received teclistamab (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline covariates of prognostic significance: refractory status, progression on last LOT, cytogenetic risk, International Staging System stage, number of prior LOT, time since diagnosis, age, and hemoglobin. Outcomes of interest included progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS); these outcomes were analyzed as time-to-event data using IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. Several sensitivity analyses were conducted. Results: After IPTW, baseline characteristics were comparable between the 2 cohorts. Patients treated with teclistamab had improved PFS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.32–0.59; P< 0.0001), TTNT (HR 0.42; 95% CI 0.31–0.58; P< 0.0001), and OS (HR 0.73; 95% CI 0.48–1.09; P= 0.13) versus assessed real-world treatments. Results were similar for all sensitivity analyses. Conclusions: Teclistamab showed improved effectiveness for PFS, TTNT, and OS, compared with real-world treatments used in patients with TCE RRMM who received ≥3 prior LOT. These findings highlight the therapeutic potential of teclistamab in patients with RRMM who have limited treatment options.

8013 Background: Tec (JNJ-64007957) is a BCMA x CD3 bispecific antibody (Ab) that redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. MajesTEC-1 is a multicohort, open-label phase 1/2 study of tec in pts with RRMM who previously received ≥3 prior lines of therapy (LOT). Results from a pooled analysis of phase 1 and phase 2 cohort A (median follow-up 7.8 mo) demonstrated an overall response rate (ORR) of 62.0% in pts with no prior anti-BCMA treatment (tx). We present initial results from cohort C, in which pts had prior exposure to an anti-BCMA tx. Methods: Eligible pts (age ≥18 y) had documented MM per IMWG criteria and had received ≥3 prior LOT including a PI, an IMiD, an anti-CD38 Ab, and an anti-BCMA tx (chimeric antigen receptor T [CAR-T] or Ab drug conjugate [ADC]). Pts were enrolled into a Simon’s stage design, receiving weekly subcutaneous tec 1.5 mg/kg preceded by step-up doses of 0.06 and 0.3 mg/kg. Primary endpoint was ORR (per IMWG 2016 criteria). AEs were graded per CTCAE v4.03; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Results: As of Sep 7, 2021, 38 pts in cohort C received tec (63% male; median age 63.5 y [range 32–82]; median prior LOT 6 [range 3–14]). 32 (84%) pts were refractory to last LOT; 25 (66%) were refractory to an anti-BCMA tx. Of 25 pts evaluated for efficacy, 16 (64%) had prior ADC, 11 (44%) prior CAR-T (2 pts received both). With median follow-up of 6.9 mo (range 0.7–8.7), ORR was 40% (95% CI 21–61). 5 pts (20%) achieved a complete response or better. The ORR (95% CI) was 38% (15–65) in ADC-exposed pts and 45% (17–77) in CAR-T–exposed pts. Most responses occurred rapidly; 7/25 pts had responses that deepened over time. Median time (range) to first and best response was 1.2 mo (0.2–4.9) and 2.1 mo (1.1–5.7), respectively. Median duration of response was not reached. The safety profile was comparable with that observed in BMCA tx-naive pts, with no new safety concerns. 16 pts (42%; grade 3/4 26%) had infections. Most common AEs (n = 38) were CRS (63%; all grade 1/2; median [range] time to CRS onset: 3 d [2–6], duration of CRS: 2 d [1–4]), neutropenia (55%; grade 3/4 50%), thrombocytopenia (42%; grade 3/4 29%), anemia (39%; grade 3/4 29%), and lymphopenia (40%; grade 3/4 37%). One pt had grade 3 ICANS that resolved with supportive care; pt remains on tx. No pts developed anti-tec Abs. Baseline BCMA expression was comparable with that observed in BCMA tx-naive pts. Updated efficacy and safety data will be presented for 40 pts. Conclusions: Initial results of serial targeting of BCMA with tec following ADC or CAR-T tx suggest a promising ORR with responses occurring early and deepening over time. A well-tolerated safety profile was observed in pts previously treated with anti-BCMA tx. Clinical trial information: NCT04557098.

Supplemental material, sj-docx-1-aim-10.1177_09645284211027892 for Regulation of serum microRNA expression by acupuncture in patients with diarrhea-predominant irritable bowel syndrome by Jing Guo, Gao Lu, Lu Chen, Hao Geng, Xiaoliang Wu, Hao Chen, Yang Li, Mengqian Yuan, Jianhua Sun and Lixia Pei in Acupuncture in Medicine

Additional file 2.

Additional file 1.

8034 Background: Tec is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in the single-arm, phase 1/2 MajesTEC-1 trial (NCT04557098) in pts with RRMM who had received ≥3 prior lines of therapy (LOT) and were TCE to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The aim of this study is to evaluate the comparative efficacy of tec versus physician’s choice of therapy, as no head-to-head trials have been conducted. Methods: An external control arm for MajesTEC-1 was created from pts in the long-term follow-up of 4 clinical trials of daratumumab (CASTOR, POLLUX, EQUULEUS, and APOLLO) who met the eligibility criteria for MajesTEC-1. These pts (N = 427) were subsequently treated with physician’s choice of therapy after discontinuing trial txs, and disease progression and best tx response were based on the investigator’s assessment. Individual pt-level data from MajesTEC-1 pts who received tec (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021 were included. Inverse probability of tx weighting (IPTW) with average tx effect on the treated population was used to adjust for imbalances in baseline covariates of prognostic significance: refractory status, progression on last LOT, cytogenetic risk, International Staging System stage, number of prior LOT, extramedullary plasmacytoma, time since diagnosis, age, and hemoglobin. Overall response rate (ORR), rate of complete response or better (≥CR), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), time to next tx (TTNT), and overall survival (OS) were assessed. For binary endpoints (ORR, ≥CR rate, ≥VGPR rate), the relative effect of tec vs physician’s choice of therapy was estimated with an odds ratio (OR) and 95% confidence interval (CI) derived from a weighted logistic regression analysis. A weighted Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% CIs for time-to-event endpoints (PFS, OS, and TTNT). Several sensitivity analyses were conducted. Results: After IPTW, baseline characteristics were comparable between the 2 cohorts. Pts treated with tec had improved outcomes vs physician’s choice of therapy: ORR (OR 4.58; 95% CI 2.83–7.53; P < 0.0001); ≥CR rate (OR 12.62; 95% CI 5.20–38.55; P< 0.0001); ≥VGPR rate (OR 11.64; 95% CI 6.49–21.98; P< 0.0001); PFS (HR 0.62; 95%CI 0.45–0.84; P= 0.0024); TTNT (HR 0.38; 95% CI 0.27–0.52; P< 0.0001); and OS (HR 0.47; 95% CI 0.32–0.69; P= 0.0001). Results were similar for all sensitivity analyses. Conclusions: Tec showed improved efficacy versus physician’s choice of therapy in all clinical outcomes, highlighting its therapeutic potential to address unmet needs in pts with TCE RRMM who received ≥3 prior LOT.

e20028 Background: Tec is a B-cell maturation antigen × CD3 bispecific antibody being evaluated in MajesTEC-1 (NCT04557098), a single-arm, phase 1/2 study in pts with RRMM who were exposed to ≥3 lines of therapy (LOT), including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. While there is currently no standard of care for treatment of pts with TCE RRMM, sel-dex is a recently approved, novel therapeutic option. Given the absence of a control arm in MajesTEC-1, we used an unanchored MAIC to compare efficacy outcomes of pts who received tec in MajesTEC-1 vs pts treated with sel-dex in the single-arm, phase 2b STORM Part 2 trial (NCT02336815). Methods: An unanchored MAIC was performed with individual pt-level data (IPD) from pts treated with tec (1.5 mg/kg weekly) in MajesTEC-1 at a clinical cutoff of Sep 7, 2021 (N = 150) and published summary-level data from pts who received sel-dex in STORM Part 2 (N = 122). After applying the STORM Part 2 eligibility criteria (penta-exposed, triple-class refractory, and refractory to last LOT), IPD from pts in MajesTEC-1 (N = 69) were weighted to match the aggregated baseline pt characteristics from STORM Part 2. Baseline characteristics of prognostic significance (refractory status, cytogenetic profile, revised International Staging System stage, presence of extramedullary disease, and number of prior LOT) were adjusted for in the analysis. Comparative efficacy of tec vs sel-dex was estimated for overall response rate (ORR), complete response or better (≥CR) rate, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). For binary endpoints (ORR and ≥CR rate), the relative effects of tec vs sel-dex were estimated using an odds ratio (OR) and 95% CI derived from a weighted logistic regression. Time-to-event endpoints (PFS, OS, and DOR) were estimated using a weighted Cox proportional hazards model. Results: After adjustment, the effective sample size (ESS) of the MajesTEC-1 cohort was 37. Baseline characteristics were balanced between the 2 cohorts. Pts treated with tec had improved ORR (OR 3.14; 95% CI 1.48–6.69; P= 0.0029), ≥CR rate (OR 16.3; 95% CI 3.5–77.1; P= 0.0004), PFS (HR 0.58; 95% CI 0.30–1.11; P= 0.1007), DOR (hazard ratio [HR] 0.04; 95% CI 0.01–0.10; P< 0.0001), and OS (HR 0.52; 95% CI 0.28–0.95; P= 0.0344) compared with sel-dex. Despite a reduced ESS that reduced limited power to detect statistically significant differences, the majority of outcomes was statistically significant in favor of tec. Conclusions : In this MAIC, tec showed significantly improved efficacy over sel-dex for all outcomes except PFS, which was numerically in favor of tec, highlighting its potential as a highly effective treatment option for pts with TCE RRMM who received ≥3 prior LOT.

8035 Background: Pts with RRMM who are TCE to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies have limited treatment options. While there is no standard of care for treatment of pts with TCE RRMM, belamaf is a recently approved, novel therapeutic option. MajesTEC-1 (NCT04557098) is a single-arm phase 1/2 study evaluating tec, a B-cell maturation antigen × CD3 bispecific antibody in pts with TCE RRMM who received ≥3 prior lines of therapy (LOT). Given the absence of a control arm in MajesTEC-1, we compared efficacy outcomes of pts who received tec at the recommended phase 2 dose in MajesTEC-1 with those of pts treated with belamaf in the phase 2 DREAMM-2 trial (NCT03525678). Methods: An unanchored MAIC was performed using individual pt-level data (IPD) from MajesTEC-1 (tec 1.5 mg/kg weekly; N = 150) at a clinical cutoff of Sep 7, 2021, and published summary-level data from pts who received the approved dose of belamaf in DREAMM-2 (2.5 mg/kg every 3 weeks; N = 97). The DREAMM-2 eligibility criteria were applied to pts from the intent-to-treat population of MajesTEC-1. IPD from MajesTEC-1 were weighted to match the aggregated DREAMM-2 baseline pt characteristics. Baseline characteristics of prognostic significance (refractory status, cytogenetic profile, International Staging System stage, presence of extramedullary disease, and number of prior LOT) were adjusted for in the analysis. Comparative efficacy of tec vs belamaf was estimated for overall response rate (ORR), complete response or better (≥CR) rate, progression-free survival (PFS), overall survival (OS), and duration of response (DOR). For binary endpoints (ORR and ≥CR rate), the relative effects of tec vs belamaf were quantified using an odds ratio (OR) and 95% CI derived from a weighted logistic regression analysis, while time-to-event endpoints (DOR, PFS, OS) were estimated using a weighted Cox proportional hazards model. Results: After adjustment, the effective sample size (ESS) of the MajesTEC-1 cohort was 33 and baseline characteristics for the reweighted MajesTEC-1 population were balanced with the DREAMM-2 population. Pts treated with tec had an improved ORR (OR 2.05; 95% CI 0.92–4.57; P= 0.0786), ≥CR rate (OR 2.13; 95% CI 0.80–5.65; P= 0.1283), PFS (HR 0.63; 95% CI 0.34–1.15; P= 0.1338), OS (HR 0.95; 95% CI 0.47–1.92; P= 0.8897), and DOR (hazard ratio [HR] 0.19; 95% CI 0.05–0.73; P= 0.0149) compared with belamaf. The reduced ESS following adjustment may account for the lack of statistical significance for most outcomes. Conclusions: These analyses demonstrated statistically improved DOR for tec vs belamaf and numerically favorable results for other outcomes, highlighting its potential as a treatment for pts with TCE RRMM who received ≥3 prior LOT.