Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Relapsed/refractory multiple myeloma (RRMM) has a poor prognosis, with limited treatment options in later lines. Immunotherapies targeting B-cell maturation antigen (BCMA), a plasma cell-specific biomarker, have shown promise in treating RRMM. ABBV-383 is a BCMA × CD3 bispecific T-cell–redirecting antibody whose mode of action may potentially decrease the incidence of cytokine release syndrome (CRS). ABBV-383 has shown promising activity in an ongoing phase 1 study in patients (pts) with RRMM (Voorhees et al. Blood 2022;140[suppl 1]:4401). Aims: This ongoing phase 1 study evaluates potential RP2D doses of 20, 40, and 60mg ABBV-383 Q3W; preliminary results from 40 and 60mg cohorts are analyzed. Due to sequential enrollment, the follow-up is longer in the 60 vs 40mg cohort at the overall study (Overall) data cutoff date. To adjust for this difference for the dose-level comparison, a 4-cycle (4-C) subset was analyzed for both cohorts, which included pts who completed ≥4 cycles or discontinued therapy in the first 4 cycles for any reason. Herein, we report updated results from the 40 and 60mg dose levels at the Overall and 4-C data cuts. Methods: Phase 1, dose-escalation and dose-expansion study (NCT03933735) of ABBV-383 in pts (≥18 yr) with RRMM (≥3 prior lines), ECOG PS ≤2, and eGFR ≥30 mL/min. Pts received ABBV-383 IV Q3W until disease progression/unacceptable toxicity. Results: As of August 16, 2022, a total of 174 pts were treated with ABBV-383 at all doses (40mg: n=55; 60mg: n=61). Median age was 68 yr (range, 35–92; 40mg: 68 [42–84]; 60mg: 68 [35–92]), median lines of prior therapy was 5 (range, 3–15; 40mg: 4 [3–11]; 60mg: 4 [3–12]) and 80% were triple-class refractory (40mg: 75%; 60mg: 82%). In total, 164 pts were included in the 4-C cutoff (40mg: n=45; 60mg: n=61). Baseline characteristics were similar in both cohorts and the median number of therapy cycles was 4 (range, 1–4) in both. At Overall cutoff, median follow-up (range) was 3.7 m (0.9–26.0) for 40mg and 15.9 m (1.1–24.9) for 60mg cohorts. At 4-C cutoff, median follow-up was 2.8 m (0.7–3.6) for 40mg and 2.8 m (0.6–13.0) for 60mg cohorts. At Overall cutoff, TEAEs were reported in 100% of pts in 40mg (G≥3 in 64% [n=35]) and 60mg (G≥3 in 80% [n=49]) cohorts. Zero (0%) and 1 (2%) pt (G4 thrombocytopenia) had a DLT during dose escalation at 40 and 60mg dose levels, respectively. Three (5%) pts at 40mg dose level and 8 (13%) at 60mg discontinued due to TEAEs. CRS occurred in 38 (69%; G≥3: n=0) pts in 40mg and 43 (70%; G≥3: n=1) in 60mg cohorts; median time to onset was 1 d (range, 1–2) for both cohorts, and median time to resolution was 2 d (1–7) and 1 d (1–10), respectively. At 4-C cutoff, TEAEs occurred in 100% of pts in 40mg (G≥3 in 62% [n=28]) and 60mg (G≥3 in 62% [n=38]) cohorts. Two (4%) pts at 40mg dose level and 4 (7%) at 60mg discontinued due to TEAEs. CRS occurred in 32 (71%; G≥3: n=0) pts in 40mg and 43 (70%; G≥3: n=1) in 60mg cohorts. Clinical responses are shown in the Table. Pharmacodynamic analyses at both dose levels showed rapid and transient increases in proinflammatory cytokines and a reduction in soluble BCMA levels over time that were associated with disease response. Summary/Conclusion: ABBV-383 monotherapy is associated with a manageable safety profile at doses of 40 and 60mg, with low incidence of TEAEs leading to discontinuation. CRS was predictable and resolved quickly with standard supportive care. Promising efficacy of ABBV-383 monotherapy was observed, with similar ORR in 40 (58%) and 60mg (61%) cohorts. These results in heavily pretreated pts with RRMM support further clinical evaluation.Keywords: Multiple myeloma, Clinical trial, Bispecific

Supplementary Figure 1. Pharmacokinetics of CPI-613 infused over 1 hour. Plasma CPI-613 levels following a 1 or 2 hour infusion shown on day 1 and day 6 on a linear scale. The number of patients in each analysis is indicated by n. **=p<0.05.

Suite à une blessure de la main occasionnée par un objet rouillé, un homme se présente à l’officine avec deux ordonnances. La première comporte des immunoglobulines, la seconde émane du chirurgien qui a suturé le tendon lésé et prévoit l’administration, en rappel, d’un vaccin combiné indiqué chez l’adulte pour la prévention conjointe de la diphtérie, du tétanos et de la poliomyélite.Anti-tetanus immunoglobulins and booster vaccine. Following an injury to his hand caused by a rusty object, a man comes to the pharmacy with two prescriptions. The first is for immunoglobins, the second is written by the surgeon who stitched the injured tendon and prescribes a combined booster vaccination indicated in adults for the prevention of diphtheria, tetanus and poliomyelitis.

Supplementary Figure 2. Differential gene expression between responders and non-responders. The top 50 genes up regulated in responders (left side) or non-responders (right side) in PBMCs from 4 responders compared to 4 non-responders taken on day 1 of week 4. Red color indicates above-mean expression, green color indicates below-mean expression. Degree of color saturation reflects the magnitude of change. R= responders, N= non-responders. FC= the mean log base 2 fold change.

e24147 Background: BIPN is a dose-limiting side effect of bortezomib therapy occurring in over three-quarters of bortezomib-treated patients and results in increased morbidity secondary to decreased quality of life and increased mortality due to treatment discontinuation or dose-reduction. Cryocompression therapy acts at the level of the nerve and does not limit bortezomib anti-tumor activity, making it ideal for clinical testing in patients with BIPN. This study evaluated the feasibility of cryocompression therapy in MM patients with BIPN. Methods: MM patients with Common Terminology Criteria for Adverse Event (CTCAE) Grade 1-3 BIPN who previously received a bortezomib-containing regimen (Arm 1) or were currently receiving a bortezomib-containing regimen (Arm 2) were enrolled at a Comprehensive Cancer Center outpatient clinic. Patients were instructed to complete daily home cryocompression treatments on non-dominant hand and foot for 30 continuous minutes for 8-weeks. Primary outcome was compliance measured by device-recorded data and defined as completion of at least 25 of 30 minutes, 60% of prescribed treatment days. Change in patient reported symptoms was assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CIPN20 questionnaire. Proportion of compliant patients was calculated. Spearman’s rank correlation coefficients were used to evaluate the association between treatment compliance and QLQ-CIPN20 scores. Here we report on Arm 1. Results: 12 patients (median age 63.9+11.8 years, 41.7% female, 66.7% white, 25.0% black) participated in Arm 1. 75% of patients were compliant. The mean proportion of treatment-compliant days was 65.8% (95% CI 46.5% – 85.0%). Patient-reported BIPN symptoms improved with QLQ-CIPN20 total and sensory sub scores of 39.2+9.2 and 22.5+4.7 at baseline, 33.7+6.2 and 19+3.5 at week 4, and 34.1+7.8 and 19.9+5.5 at week 8. This accounted for a statistically significant decline in total QLQ-CIPN20 score at week 4 (-5.9+9.1, p = 0.035), week 8 (-4.6+5.0, p = 0.020), and sensory sub score at week 4 (-3.5+3.4, p = 0.008) and week 8 (-2.6+3.5, p = 0.050). There was no correlation between compliance and change in total QLQ-CIPN20 score (r = -0.31, p = 0.380) or sensory sub score (r = -.054, p = 0.109) in the per protocol analysis (N = 10). Using a last-time-point available analysis, no correlation was observed for total QLQ-CIPN20 score (r = -0.44, p = 0.149) but a moderate-to-strong inverse correlation was observed between amount of cryocompression use and change in QLQ-CIPN20 sensory sub score (r = -0.62, p = 0.031). Conclusions: Cryocompression therapy is feasible in MM patients with BIPN who previously received a bortezomib-containing regimen. The observed biologic gradient with greater improvement in patient-reported sensory neuropathy with longer duration of cryocompression treatment supports the rationale and further study. Clinical trial information: NCT03870451 .

Background: Infections in patients with multiple myeloma are a frequent cause of morbidity and mortality. Intravenous immunoglobulin (IVIG) replacement is a preventative strategy for infection risk reduction. The NCCN guidelines recommend IVIG therapy should be considered in the setting of recurrent serious infection and/or hypogammaglobinemia. The IMWG suggests a targeted use, limiting replacement to patients with IgG concentrations less than 400mg/dl and who have serious recurrent encapsulated bacterial infections. In this study, we sought to describe patterns of IVIG use prior to and during the COVID-19 epidemic. Methods: In this cross-section study, we sought to describe real-world patterns of outpatient IVIG use before and during the COVID-19 pandemic using the IBM MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits (COB, a.k.a. MDCR) databases. MarketScan is an administrative database of diagnostic and treatment data for more than 30 million commercially insured individuals in the United States. Patients included in this study had private insurance or were enrolled in a Medicare advantage plan. IVIG administration data was grouped by patient age, sex, geographic region, and metropolitan area defined by the Census Metropolitan Statistical Area,. Pre-pandemic time period is defined as the time prior to March 2020. Results: Our study showed changes in patterns of IVIG use with respect to patient age, sex, geographic region, and location of care delivery. A total of 12,893 patients were identified with multiple myeloma during this study period. Patients greater than age 65 made up 31.3% of the cohort. Location of IVIG administration was outpatient hospital (32.6%), Office (40.2%), Patient home (14.9%) and other (0.9%). Pre-pandemic IVIG usage rate in this cohort was 3.37 IVIG administrations per 100 patients studied compared to post-pandemic usage rate increased to 3.6 per 100 patients (p=0.038). A significant increase in utilization is noted by age with usage rate in patients over age 65 increasing from 1.96 to 2.54 (p<0.001). Prior to the pandemic, usage rate for males was 2.2 and increased to 2.51 after the pandemic (p<0.001). For females, usage rate also increased from 2.42 to 2.58 (p=0.07). Changes in utilization also occurred regionally with increased use in the Northeast and West. Usage rates in the Northeast prior to the pandemic were 2.37 compared to 3.28 IVIG administration (p<0.001). Similarly, pre-pandemic utilization rates in the West were 2.55 and increased to 3.21 (p<0.001). Usage rates were stable in the North Central region, only increasing from 2.09 to 2.15 (p=0.54). Interestingly, usage rates decreased slightly in the Southern region from 2.32 to 2.24 post pandemic (p=0.38). Metropolitan service areas saw a slight increase in utilization from 2.41 to 2.56 (p=0.06). However, non-metropolitan service areas had an increase from 2.1 to 2.56 (p<0.001). Conclusions: This study describes the variation in outpatient IVIG use by age, geographic region, sex and location of treatment before and during the COVID-19 pandemic. During the COVID-19 pandemic, there was significant uncertainty regarding optimal infection risk mitigation strategies for patients with multiple myeloma. In this real-world review of clinical practice patterns, variations in outpatient use of IVIG can be seen to vary most based on geographic region and patient age. Statistically significant increases are also seen in males and in non-metropolitan areas. Patients in regions impacted earliest and hardest by increase in COVID-19 infections saw the greatest increase in the use of IVIG while other regions saw stable or decreased utilization. Additionally, patients over age 65, who were at greatest risk for negative outcomes of COVID-19 infections saw the greatest increase in utilization compared to pre-pandemic rates. In the post pandemic time period, patients over age 65 continued to have statistically significant increased rates of utilization while patients less than age 65 also increased rates of utilization that was not statistically significantly increased. This study is limited by lack of clinical information including COVID 19 infection status and concomitant myeloma therapy. The variation in utilization of IVIG illustrates the need for prospective studies to guide its use.

Figure S1. Dose escalation schema. Figure S2. Acetyl-CoA synthetase is expressed in OCI-AML3 and MFL2 cells. Figure S3 Acetate and methyl-succinate rescue of CPI-613 cytotoxicity. Figure S4. Treatment schema. Figure S5. Efficacy of HiDAC, mitoxantrone and CPI-613. Figure S6. Baseline bone marrow mononuclear cell gene expression profiles of responders (n=10) versus nonresponders (n=7). Figure S7. SOD2 expression levels are higher in non-responders Figure S8. SOD2 confers resistance to CPI-613. Figure S9. Mutational analysis from RNA sequence data of baseline marrow samples. Supplemental Table 1. Dose and Response by Patient Supplementary Table 2. Gene ontology enrichment analysis of genes overexpressed in responding patients

LBA4 Background: Optimal use of triplet/quadruplet induction, ASCT, and R-based maintenance in patients (pts) with NDMM who are eligible for transplant continues to evolve. The IFM 2009 trial, which used R maintenance for 1 year (y), showed progression-free survival (PFS; median, 35.0 vs. 47.3 months [mos]) but no overall survival benefit (OS; 60 vs. 62% at 8 y; median follow-up, 89.8 mos) with RVd + ASCT vs. RVd alone in the setting of multiple effective options at relapse, including ASCT at first relapse in 77% of pts (Attal M et al, N Engl J Med 2017; Perrot A et al, ASH 2020). We report primary data from our US DETERMINATION trial, which used R maintenance until progression. Methods: Pts with NDMM aged 18-65 y were randomly assigned to receive 3 RVd cycles, stem cell mobilization, and then 5 more RVd cycles (Arm A) or IV melphalan 200 mg/m2 + ASCT and 2 RVd cycles (Arm B). Each 21-d RVd cycle comprised PO R 25 mg (d 1-14), IV/SC bortezomib 1.3 mg/m2 (d 1, 4, 8, 11), and PO dexamethasone 20/10 mg (cycles 1-3/≥ 4; d 1, 2, 4, 5, 8, 9, 11, 12). Both arms received R 10-15 mg/d maintenance until progression or intolerance. The primary endpoint was PFS (90% power to detect PFS hazard ratio [HR] of 1.43 [Arm A vs. B] with α = 0.05 on stratified two-sided log-rank test; full information: 329 events in 720 pts). Data cut-off was Dec 10, 2021. Results: 357 and 365 pts were randomly assigned to Arms A and B, respectively; median age was 57 and 55 y, 14% and 13% had ISS stage III MM, and 18% each had high-risk cytogenetics [t(4;14), t(14;16), del17p]. In the respective arms, 291 and 290 pts received R maintenance for a median duration of 36 and 41 mos. After median follow-up of 76 mos and 328 events, median PFS was 46.2 vs. 67.6 mos in Arm A vs. B (HR 1.53; 95% CI, 1.23–1.91; p < .0001). Best responses in pts assessed to date were 52 vs. 62% ≥ CR (p = .006), 79 vs. 83% ≥ VGPR and 94 vs. 96% ≥ PR; in 251 evaluable pts, rate of MRD negativity (10-5) was 37.3 vs. 52.1% (p = .021) within 1 y of maintenance. 63 vs. 53% of pts have received subsequent treatment; of Arm A, 22% had ASCT as first non-protocol therapy. With 90 vs. 88 pts having died in Arm A vs. B, 4-y OS was 84% (95% CI, 80–88%) vs. 85% (95% CI, 81–88%); HR 1.10 (95% CI, 0.81–1.47; p = .274). Grade ≥ 3 related adverse events were less common in Arm A vs. B (78 vs. 94%; hematologic: 61 vs. 90%, p < .0001); 10 vs. 11% had secondary malignancies (ALL, 7 vs. 3 pts, p = .22; AML/MDS, 0 vs. 10 pts, p = .002). Difference in mean change from baseline in EORTC QLQ-C30 global health status score was < 10 points throughout treatment except at RVd cycle 5 vs. post-ASCT (compliance rate, 75% vs. 55%; mean change +3.0 vs. –11.1; p < .0001). Whole-genome sequencing, additional QOL, and correlative analyses are ongoing. Conclusions: RVd ± ASCT and R maintenance to progression resulted in the longest median PFS reported for each approach, and a highly significant 21.4-mo gain in median PFS benefit using RVd + ASCT. No OS advantage has been observed to date. Clinical trial information: NCT01208662.

Background: Talquetamab (tal; JNJ-64407564) is a first-in-class, bispecific IgG4 antibody that binds both to G protein-coupled receptor family C group 5 member D (GPRC5D), a receptor highly expressed on malignant plasma cells but with limited expression in healthy tissue, and CD3 to mediate T-cell–activated lysis of GPRC5D+ multiple myeloma (MM) cells. Daratumumab (dara) is an anti-CD38 mAb with direct on-tumor and immunomodulatory actions. Initial clinical results from the phase 1b multicohort TRIMM-2 study identified the recommended phase 2 doses (RP2Ds) of tal as 400 μg/kg weekly or 800 μg/kg Q2W and support the combination of tal + dara for the treatment of RRMM, with manageable safety, no overlapping toxicities, and promising efficacy. Aims: Here we report updated results for both RP2Ds of tal + dara in TRIMM-2 with additional patients (pts) and longer follow-up. Methods: Eligible MM pts (aged ≥18 years) had received ≥3 prior lines of therapy (LOT; including a PI and IMiD) or were double refractory to a PI and an IMiD, and could not have received anti-CD38 therapy within 90 days. Pts received dara SC 1800 mg per approved schedule and tal (400 μg/kg weekly or 800 μg/kg Q2W) with step-up dosing. The primary objectives were to identify the RP2D(s) of tal for combination therapy and evaluate safety of the combination. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Responses were assessed by IMWG criteria. Results: At data cutoff (Jan 13, 2022, N=46), median follow-up was 4.0 months (range 0.4-16.3), median age was 65 years (range 47-81), and 48% were female. Pts received a median of 5 prior LOT (range 2-16); 83% were triple-class exposed, 61% penta-drug exposed, 37% anti-BCMA non–CAR-T exposed, and 4% anti-BCMA CAR-T exposed. 96% of pts had ≥1 AE (gr 3/4: 67%). The most frequently reported AEs (≥30% across tal + dara cohorts) were CRS (65%; all gr 1/2; median time to onset: 2 days; median duration: 2 days), dysgeusia (57%), thrombocytopenia (35%; gr 3/4: 20%), anemia (39%; gr 3/4: 20%), and dry mouth (44%). Infections occurred in 50% of pts (gr 3/4: 13%). Skin disorders were reported in 72% of pts (gr 3/4: 11%): skin exfoliation in 26% (all gr 1/2) and nail disorders in 11% (all gr 1/2). Two ICANS events were reported in the 800 Q2W group (both gr 1 and resolved within 1 day). 3 pts discontinued due to AEs. Response rates were consistent across both RP2Ds supporting their equivalence (Table). Median time to first response across dosing cohorts was 0.95 months (range 0.9-9.7); median duration of response was not reached. Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed with tal + dara, supporting potential synergy of the combination in pts with prior anti-CD38 exposure. Updated results will be presented. Image:Summary/Conclusion: Longer follow-up with additional patients shows comparable efficacy and safety across both RP2Ds, with no new safety signals, strengthening the benefit-risk profile of tal + dara as a novel immunotherapy-based approach for heavily pretreated pts with RRMM.

BACKGROUND In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

Background: Teclistamab (JNJ-64007957) is a B-cell maturation antigen (BCMA) × CD3 T-cell redirecting bispecific antibody currently under investigation in patients with relapsed/refractory multiple myeloma (RRMM). Daratumumab is a CD38-targeting monoclonal antibody with direct on-tumor and immunomodulatory mechanisms of action. The preliminary results from the phase 1b multicohort TRIMM-2 study showed tolerable safety with no overlapping toxicities, and encouraging efficacy, supporting the combination of teclistamab with daratumumab for the treatment of RRMM. Aims: We report updated results from the TRIMM-2 study with additional patients and longer follow-up. Methods: Eligible patients were ≥18 years of age with a MM diagnosis and previously treated with ≥3 prior lines of therapy (including a proteosome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double-refractory to a PI and IMiD. Patients who had received anti-CD38 therapy ≤90 days prior were excluded. Written informed consent was obtained from all eligible patients. Patients received subcutaneous (SC) daratumumab 1800 mg per approved schedule and teclistamab SC 1.5–3 mg/kg once weekly or every 2 weeks. Primary objectives of the study were to identify the recommended phase 2 dose for the teclistamab and daratumumab combination and to assess safety of the combination. Responses were assessed by IMWG criteria. Adverse events (AEs) were graded per CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), which were graded per ASTCT guidelines. Results: At the Jan 13, 2022 data cutoff, the median follow-up was 7.2 months (range 0.1–16.6). Among the safety population (N=46), 52% were females, and the median age was 67 years (range 50–79). Patients received a median of 6 prior lines of therapy (range 2–17); 74% of patients were triple-class exposed; 63% were penta-drug exposed, and 15% were anti-BCMA exposed. Overall, 91% of patients had ≥1 AE of any grade; 78% had grade 3/4 AEs. The most common AE was CRS (61%; all grade 1/2); median time to onset was 2 days and median duration was 2 days. Other AEs included neutropenia (54%; grade 3/4 50%), anemia (46%; grade 3/4 28%), thrombocytopenia (33%; grade 3/4 28%), and diarrhea (33%; grade 3/4 2%). Infections occurred in 29 patients (63%; grade 3/4 28%). One patient had grade 1 ICANS that was fully resolved. Among 37 response-evaluable patients, the overall response rate was 78% (29/37); 27 patients (73%) had very good partial response (VGPR) or better (Table). While the median duration of response was not reached, median time to first response across dosing cohorts was 1.0 month (range 0.9–2.8). Upregulation of CD38+/CD8+ T cells and proinflammatory cytokines was observed after teclistamab dosing in combination with daratumumab, supporting potential synergy of the combination in patients with prior anti-CD38 exposure. Updated results will be presented. Image:Summary/Conclusion: Teclistamab in combination with daratumumab is a novel immunotherapy approach that may yield improved clinical efficacy in heavily pretreated patients with RRMM.