Pb2134: bcma-targeted therapies in patients with relapsed/refractory multiple myeloma after allogeneic stem cell transplantation – a single center experience

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: In patients with multiple myeloma refractory to immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (CD38-Abs), prognosis is particularly poor. In this situation, allogeneic stem cell transplantation (alloSCT) may be considered for selected patients, although disease progression after allogeneic SCT is a frequent problem. B-Cell Maturation Antigen (BCMA)-targeted agents are a promising therapeutic option for these heavily pretreated patients. In Austria, the antibody drug conjugate (ADC) Belantamab Mafodotin, and Teclistamab, a T-cell redirecting bispecific antibody targeting BCMA, are currently available. Aims: We report a case series of seven penta-refractory (CD38-Ab, 2 IMiDs, 2 PIs) myeloma patients who received BCMA-targeted therapies (Belantamab Mafodotin and/or Teclistamab) after alloSCT. Methods: All patients at our center who received BCMA-targeted therapies after alloSCT were included and retrospectively analyzed. Cytogenetic risk profile and diagnostics for extramedullary disease (EMD) are available for all patients. Prior lines of therapy (LoT), refractoriness to IMiDs, PIs and CD38-Abs, timing of autologous SCT(s) and alloSCT were recorded. Regarding BCMA-directed therapies, best response, duration of response, and side effects were documented. Results: Seven patients with multiple myeloma received BCMA-targeted therapies for relapse after alloSCT. All 7 patients were penta-refractory, 6 of 7 had extensive EMD, and 4 of 7 had high-risk cytogenetics. 3 and 4 patients had one and two previous autologous SCT, respectively. Belantamab was used in 4 patients, and Teclistamab in 5 (2 patients received both therapies). The median number of prior LoT was 5 (range, 4-7) for Belantamab and 7 (range, 5-9) for Teclistamab, respectively. Median time between alloSCT and first BCMA-targeted therapy was 22.9 (range, 2.4-38.0) months. Because most of the alloSCT were performed in the pre-BCMA era, only one patient received BCMA therapy (both agents) before alloSCT, without response. For this patient, response assessment of Teclistamab retreatment after alloSCT is pending at the time of abstract submission. Of the 4 patients treated with Belantamab, one achieved a partial response (PR) and was treated for 6.7 months; the other 3 patients experienced only short-lasting stable disease (SD) or no response. All 4 evaluable patients on Teclistamab therapy have shown a sustained response: 2 stringent complete responses (sCR), 1 very good PR (VGPR), and 1 PR, lasting for 10.2, 7.4, 6.6 and 3.1 months, respectively, so far. The side effects of teclistamab were manageable, only one of the patients developed cytokine release syndrome (CRS) grade 1 and immune effector cell-associated neurotoxicity syndrome (ICANS) grade 2. Both completely recovered. Infections were frequent, but no fatal events have occurred (2 grade 3 infections, all others grade 1-2). No Graft versus Host Disease (GvHD) has been observed in any of the patients during therapy with teclistamab. Summary/Conclusion: BCMA-targeted therapies are well tolerated in heavily pretreated myeloma patients, even after alloSCT and without inducing GvHD despite T-cell activation. In this difficult-to-treat patient group, in which extensive EMD frequently occurs, especially Teclistamab appears to be a potent BCMA-targeting therapeutic option. The evaluated patients showed surprisingly deep responses despite multiple prior LoT and extensive EMD. A possible explanation for these remarkable responses could be the less exhausted, donor-derived T-cell system in patients after alloSCT, providing a reasonable basis for T-cell redirecting therapies even in these heavily pretreated patients. Keywords: Myeloma, B-cell maturation antigen, Allogeneic stem cell transplant