Cellular and T cell engager Immunotherapy

Category: Cellular and T cell engager Immunotherapy

Severe Tumor Flare Pain Syndrome During Step-Up Dosing of Teclistamab in High-Risk Relapsed/Refractory Multiple Myeloma

(PA-018) Severe Tumor Flare Pain Syndrome During Step-Up Dosing of Teclistamab in High-Risk Relapsed/Refractory Multiple Myeloma

Wednesday, September 17, 2025

Gaspard Jadot, MD

Fellow
Hôpital Maisonneuve-Rosemont

Introduction: Teclistamab (TEC) is the first approved B-cell maturation antigen × CD3 bispecific antibody for the treatment of triple-class exposed relapsed/refractory multiple myeloma (RRMM). In the MajesTEC-1 trial, TEC produced profound and durable responses with a manageable safety profile, with 3.6% of patients complaining debilitating bone pain episodes. In contrast, we have observed a higher frequency of such events in our outpatient setting, particularly during the step-up dosing (SUD) phase. This study aimed to assess the incidence, presentation, and outcomes of tumor flare pain syndrome associated with TEC.

Methods: We conducted a retrospective, single-center analysis of patients ≥18 years of age with RRMM treated with TEC in the outpatient setting. Tocilizumab prophylaxis 8 mg/kg was administered before SUD 1 of TEC. The SUD regimen consisted of 0.06 mg/kg subcutaneously (SC) on day 1, 0.3 mg/kg SC on day 3, and 1.5 mg/kg SC on day 5. TEC 1.5 mg/kg SC was then given weekly, until MM progression or unacceptable toxicity. The primary endpoint was the incidence of severe tumor flare pain syndrome occurring during SUD (equivalent to bone pain grade ≥3 per CTCAE v5.0).

Results: A total of 49 patients who received teclistamab were reviewed. Among them, we identified 7 subjects (5 males, 2 females) who developed tumor flare pain syndrome during SUD, including 3 patients with plasmablastic myeloma and 1 with plasma cell leukemia. Median age was 63 years (39-79 years). Each of these patients had extramedullary disease at the beginning of TEC administration. One patient experienced grade 2 CRS, none had ICANS. Median time until the onset of tumor flare pain syndrome was 3 days (range: 2-4) after the first TEC dose, and the median duration was 5 days (range: 2 to 7). Tumor flare pain syndrome only occurred during SUD. Imaging finding on PET-CT or CT-scan included (in contrast with baseline imaging) progression of bone lesions (n=4), progression of extramedullary plasmacytomas (lung and peritoneum; n=2) and a new muscular lesion in one patient. Four patients required hospitalization for pain control. All received opioids, and 4 (n=4/7) were relieved by dexamethasone 10 mg PO/IV q 6h. All 7 patients were evaluable for clinical response; with complete response in 2, partial response in 2, and stable disease in 3.

Conclusions: Clinicians should be aware that tumor flare pain syndrome is an underreported manifestation occurring during the SUD phase of T-cell redirected therapies. It is associated with intense pain sometimes requiring hospitalization and may mimic disease progression radiographically (pseudoprogression). Dexamethasone seems most beneficial for pain management, but prospective studies are needed to guide optimal relief strategies.