Real-World Outcomes of Patients with Relapsed/Refractory Multiple Myeloma Treated with Teclistamab and Talquetamab; A Multicenter Analysis from the Greek Myeloma Study Group
Authors: Ntanasis-Stathopoulos Ioannis , Katodrytou Eirini , Hatjiharissi Evdoxia , Spanoudakis Emmanouil , Douka Vasiliki , Fotiou Despina , Labropoulou Vasiliki , Dalampira Dimitra , Spiliopoulou Vasiliki , Papadopoulou Theodosia , Christoulas Dimitrios , Malandrakis Panagiotis , Bouchla Anthi , Pappa Vasiliki , Kastritis Efstathios , Terpos Evangelos , Dimopoulos Meletios , Gavriatopoulou Maria 
Published: December 2024

Introduction: The bispecific antibodies teclistamab (TEC) and talquetamab (TAL) have been recently approved in patients with relapsed/refractory multiple myeloma (RRMM).
Methods: We retrospectively evaluated the efficacy and safety outcomes of patients with RRMM treated with the approved schedule of TEC or TAL at 8 Greek centers until 30/06/2024.
Results: 35 patients were included; 24 on TEC (median age 66.5 years, range 44-85, 45.8% females) and 11 on TAL (57 years, 50-60, 18.2% females). 10 (41.7%) and 1 (9.1%) were primary refractory, whereas 13 (54.2%) and 10 (90.9%) were penta-refractory, respectively. The patients had received a median of 5 (range 3-11) and 7 (5-11) prior lines of treatment, respectively. 9 (37.5%) and 6 patients (54.5%) had extramedullary disease (EMD), respectively.
After a median of 8 and 7 cycles (range 3-23 and 2-17), respectively, best responses included 7 (33.4%) complete response (CR) or better, 3 (12.5%) very good partial response (VGPR) and 7 (29.2%) partial response (PR) for TEC and 1 (9.1%) CR or better, 2 (18.2%) VGPR, 2 (18.2) PR, 1 (9.1%) minor response (MR) and 3 (27.3%) stable disease (SD) for TAL. The median time to first response was 36 (range 20-120) and 42 (15-67) days and the median time to best response was 56.5 (range 20-211) and 56 (15-194) days, respectively. 3/7 patients with EMD on TEC responded (42.9%) and 2/6 on TAL (33.3%).
14 patients (58.3%) on TEC are still ongoing treatment in remission, 1 (4.2%) is off treatment but in remission, while 5 (20.8%) have discontinued due to progressive disease (PD) (5%) and 4 (23.6%) have died (3 due to PD, 1 due to COVID-19); two (8.3%) were lost to follow-up. For TAL, 5 patients (45.5%) are still undergoing treatment on remission, whereas 6 (54.5%) have died due to PD.
At a median follow-up of 4.6 months (range 0.2-13.5) for TEC and 7.8 months (1.1, 19.8) for TAL, the median progression-free survival (PFS) was not reached (NR) and was 6.9 (95% CI: 3.87, NA) months, respectively. Median overall survival (OS) was NR for TEC, while it was 11.5 months (95% CI: 7.8, NA) for TAL. There were no significant differences in PFS for each treatment group when stratified by the presence of high-risk cytogenetics, ISS stage, penta-refractory status or extramedullary disease.
Every patient was hospitalized at least for the initial administration of the drug. The median days of hospitalization were 9 (range 2-45) and 10 (9-22), respectively. Five patients on TEC (20.8%) and 3 on TAL (27.3%) were required to be re-admitted, mainly due to infections. The median hospitalization days for re-admitted patients were 5 (range 2-10) and 7 (4-9), respectively.
Eight patients (33.3%) on TEC and 8 patients (72.7%) on TAL developed grade 1-5 infections (mainly bacterial and viral) with the first being at a median of 3 (range 1-15) and 1 (range 1-5) cycles, respectively. Five of infected patients on TEC and the 6 on TAL required hospitalization with a median of 5 (range 4-10) and 7 (range 5-45) days until resolution. There was no association between baseline neutrophil or leukocyte levels and infection occurrence.
Therapy-induced CRS was documented in 15 (62.5%) TEC and 7 (63.6%) TAL patients. There were 5 (20.8%) and 7 (63.6%) incidences of CRS after dose step-up. The median grade for both groups was 1 (range 1-3). The median time to CRS onset for both groups was 1.5 and 1 day (ranges 1-5 and 1-1) and the median time to resolution for both groups was 1 day (ranges 1-5 and 1-2). The main treatment of choice in both cohorts was tocilizumab (40.0% and 42.9%). There was only one case of Immune effector cell-associated neurotoxicity syndrome (ICANS) in the TEC group.
Hypogammaglobulinemia was common even at treatment initiation, as it was present in 16 (66.7%) and 3 (27.3%) patients for TEC and TAL groups, respectively. There were also 10 (41.7%) cases during TEC treatment. After a median of 4 months (range 1-8) on Ig administration, 9 patients (90.0%) recovered. Moreover, there were 7 (29.2%) and 5 (45.5%) cases of grade 3 or 4 neutropenia and 8 (33.3%) and 5 (45.5%) cases of grade 3 or 4 thrombocytopenia, respectively.
Dermatological complications were prevalent mainly in the TAL group, with 3 (12.5%) cases of grade 2 rash and 4 (36.4%) nail changes. There were 3 (12.5%) cases of grade 1-3 rash in the TEC group.
Conclusion: Real-world outcomes confirm the efficacy and safety profile of TEC and TAL in RRMM comparable to clinical trials.