Effect of Consolidation with Allogeneic Hematopoietic Cell Transplant Versus No Consolidation in Patients with Non-Hodgkin Lymphomas Treated with Bispecific Antibodies

Background: Bispecific antibodies (BsAb) are an effective salvage therapy for relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL). Patients (pts) achieving partial (PR) or complete response (CR) with BsAbs can experience prolonged duration of response, raising questions about the role of allogeneic hematopoietic cell transplantation (HSCT) as consolidation after BsAbs. Our aim is to compare the impact of HSCT consolidation in pts treated with BsAb versus a non-consolidation strategy.

Methods: We conducted a multicentric, retrospective study including adult pts with R/R B-NHL treated with BsAbs as last line of therapy and consolidated with HSCT. A control cohort of adult pts with R/R B-NHL treated with BsAbs who did not receive HSCT from a single institution was used. All pts received BsAb from April 2016 to July 2024 and had at least 3 lines of therapy before BsAb administration. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), non-relapse mortality (NRM) and relapse incidence/progression of disease (Rl/POD). The analysis started from the day of administration of the first dose of BsAb. A preplanned subanalysis for pts who reached PR/CR during BsAbs treatment was performed.

Results: Seventy-eight pts were enrolled. Forty-one (52.6%) pts received HSCT consolidation as per physician decision. The two groups (HSCT versus no consolidation) significantly differed in median age at BsAb administration (57 [range 22-71] vs 69 years [range 38-82], p=0.001), primary refractory disease (16 [39.0%] vs 8 [21.6%], p=0.001), prior administration of chimeric antigen T-cell receptor (20 [48.8%] vs 1 [2.7%], p<0.001), number of median lines at which BsAb was administered (4 [range 3-11] vs 3 [range 3-12], p=0.001) and type of administered BsAb (glofitamab 21 [51.2%] vs 17 [45.9%], epcoritamab 7 [17.1%] vs 20 [50.4%], mosunetuzumab 1 [2.4%] vs 0, ondronextamab 11 [26.8%] vs 0, BsAb antiCD22-CD3 1 [2.4%] vs 0, p<0.001). Median duration of BsAb treatment was 4.4 months (range 1.4-10.8) vs 3.5 months (range 0-48.4, p=0.620). Median number of BsAb administered doses was 12 (range 4-24) vs 11 (range 1-68)(p=0.394).

Of the 41 pts who proceeded to HSCT consolidation, 36 (87.8%) were in CR, 4 (9.8%) in PR and 1 (2.4%) in progressive disease (PD) before transplant. Median time from last BsAb dose to HSCT was 35 days (range 13-203). Type of donor was matched unrelated in 16 (39.0%), haploidentical in 16 (39.0%) and matched related in 9 (22.0%) pts. Thirty-eight (91.7%) pts received reduced intensity conditioning protocols, and 30 (73.2%) received post-transplant cyclophosphamide as graft-versus-host-disease prophylaxis.

Of the 37 pts who did not receive HSCT, overall response rate was 54% (n = 20) (CR rate 48.6% [n = 18]). Eight (21.6%) pts received a fixed number of doses of BsAb as per protocol. Early discontinuation of BsAb occurred in 25/29 pts (86.2%): 15 (40.5%) due to RI/POD, 8 (21.6%) due to toxicity and 2 (5.4%) due to other causes. Four pts (10.8%) had ongoing treatment at analysis. All grade cytokine release syndrome occurred in 18 pts (48.6%) with all being grade 1 or 2. All grade immune effector cell-associated neurotoxicity syndrome occurred in 2 pts (< grade 3). The median time to best response was 41 days (range 27-166). Median duration of best response was 23.1 months (range 0.9-77).

Median follow-up among survivors from the whole series was 20.6 months (22.3 months[range 4.6-86.4] for the HSCT cohort vs 16.6 months [range 0.7-76.8] for the not consolidated group). At 1-year, no differences were observed in univariate analysis in terms of PFS (61.8% vs 53.8%, p=0.077), OS (85.2% vs 59%, p=0.266) and NRM (15.9% vs 2.8%, p=0.122) among HSCT and no-consolidation cohorts. A lower RI/POD was observed in the HSCT group (8.5% vs 43.3%, p<0.001). In the subanalysis including only pts achieving PR/CR before HSCT (n=40) or during BsAb treatment without consolidation (n=20), no differences in terms of PFS (60.7 vs 84.7%, p=0.379), OS (84.8% vs 90%, p=0.437) and RI/POD (8.7% vs 15.3%, p=0.228) were found. However, a higher NRM was observed after HSCT(13.4% vs 0%, p=0.026).

Conclusions: HSCT consolidation does not seem to be associated with improved survival outcomes, especially for pts reaching a PR or CR during BsAb treatment. These results should be confirmed in a larger study population with a prolonged follow-up.