Single Center Real World Experience of Talquetamab in Patients with Relapsed and Refractory Multiple Myeloma
Authors: Grajales-Cruz Ariel F. , Graeter Allison , Hansen Doris K. , Castaneda Omar , Vazquez-Martinez Mariola A , Modukuri Shrikar , De Avila Gabriel , Denson Ariel , Fadul Julia , Tobon Katherine , Blue Brandon , Lopez Blanca , Harvey Kristy , Melnick Parker , Thapa Shrinjaya B , Ionescu Filip , Liu Hien , Ochoa-Bayona Jose L. , Freeman Ciara Louise , Locke Frederick , Nishihori Taiga , Shain Kenneth H. , Baz Rachid , Alsina Melissa 
Published: December 2024

Background
Talquetamab (Talq) is a GPRC5D bispecific antibody approved for triple class exposed patients (pts) with relapsed and refractory multiple myeloma (RRMM), after 4 prior lines of therapy (LOT). MonumenTAL-1, a phase I/II study, demonstrated an ORR of 71.7% at a dose of 0.8mg/kg subcutaneous every 2 weeks (Q2W) after step-up doses. Here, we present a single center, real-world experience (RWE) supporting the safety and efficacy of Talq in RRMM pts.
Methods
This retrospective analysis at Moffitt Cancer Center evaluated pts with RRMM that were treated with Talq at a dose of 0.8mg/kg subcutaneous Q2W after step-up doses between September 2023 and July 1, 2024. CRS and ICANS were graded per ASTCT consensus criteria, while responses were graded based on the IMWG response criteria.
Results
A total of 54 pts was treated with Talq in our institution; 39 pts with intent to treat until disease progression or intolerable adverse events, and 15 pts with intent to bridge to CAR-T with only 1 cycle of therapy. Median age was 66 years (range 39-89), 44.4% (n=24) were male, and 24.1% (n=13) had an ECOG PS ≥2. 70.4% (n=38) had high risk cytogenetics (defined as del17, t(4;14), t(14;16), and gain 1q).
Pts were heavily pretreated with a median of 7 (4-11) prior lines of therapy. 85.2% (n = 46) were triple-class refractory, and 38.9% (n=21) were penta-class refractory. 64.8% (n=35) received prior B-cell maturation antigen targeted therapies (BCMA-TT). 66.7% (n=36) of pts did not meet inclusion criteria for the MonumenTAL-1 study, including 44.4% (n = 16) for cytopenia, 27.8% (n=10) for renal dysfunction, and 30.6% (n=11) for ECOG ≥2. With a median follow up of 5.04 (0.3-11.6) months, progression free survival (PFS) and overall survival (OS) have not been reached. Overall response rate was 75.9% (n=41) with 18 pts (33.3%) achieving a complete response or better (≥CR). Ten pts (18.5%) achieved minimal residual disease (MRD) negativity by next generation sequencing (NGS). Overall Response Rate (ORR) was 76.9% (n=30/39) among pts receiving Talq as primary treatment, with 18 pts (46.2%) achieving a complete response (CR) or better. ORR was 73.3% (n=11/15) in pts receiving Talq as bridging with 3 pts (18.8%) achieving a very good partial response (VGPR) and 50% (n=8) achieving a partial response (PR).
CRS occurred in 59.3% (n=32) of pts, (16 pts with grade 1, 15 pts with grade 2, and only 1 pt with grade 4), with 35.2% (n=19) requiring Tocilizumab. Median time to onset of CRS was 4.4 (1-20) days after the first dose. Of the 15 pts receiving Talq as a bridge to CAR-T 11 (73.3%) had CRS. 14.8% (n=8) pts had ICANS, (4 pts with grade 1, 3 pts with grade 2, and 1 pt with grade 3). Infections were seen in 16 (29.6%) pts. Dysgeusia, weight loss, skin-related changes, and nail-related were seen in 74.1% (n=40), 44.2% (n=24), 59.3% (n=32), 38.9% (n=21) of pts respectively. Pts bridged with Talq had more dysgeusia than those primary treated, but weight loss was comparable.
Conclusions
This single center real world safety and efficacy analysis was comparable to that reported in the MonumenTAL-1 study. Pts receiving Talq as a bridge to CART seem to have higher grades of CRS and dysgeusia, while responses were not as deep as those that were primarily treated with Talq. The difference in depth of response can be explained by the shorter course of therapy for those who receive talq for bridging as opposed to primary therapy. In addition, those patients had a higher tumor burden, and this can explain possibly the higher rate of CRS. Longer follow up, larger numbers, and further biological characterization are needed to properly understand the role of Talq as bridging therapy for CART.
*AFG, AG, DKH are co-first authors