LY-02. Treatment strategy of patients with relapsed and refractory aggressive B-cell non-Hodgkin lymphoma
Liudmila V. Fedorova, Olesya G. Smykova, Andrey M. Chekalov, Marina O. Popova, Vladislav V. Markelov, Elena V. Kondakova, Ivan S. Moiseev, Kirill V. Lepik, Natalia B. Mikhailova, Alexander D. Kulagin
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
Contact: Dr. Liudmila V. Fedorova, phone: +7 (921) 770-49-92, e-mail: Lucyfed3@gmail.com
Up to 40-50% of patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL) remain refractory to treatment, or develop relapse (r/r) after 1-2 lines of therapy. The prognosis of this patient’s group remains unfavorable. However, the emergence of new methods of targeted drug and immunotherapy (polatuzumab vedotin, Pola; glofitamab) may improve both progression-free survival (PFS) and overall survival (OS) rates in the patients with r/r B-NHL. The aim of our study was to suggest the treatment strategy for this population of patients, as well as to determine place for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Patients and methods
The study included 28 patients (pts) with r/r B-NHL treated with a bispecific drug (anti-CD20/anti-CD3) glofitamab (G) within Russian Early Access Program. G was administered at escalated schedule, i.e., 2.5 mg D8C1, 10 mg D15C1, 30 mg D1C2-12. Anti-CD20 antibody was administered 1 week before the G therapy was started. Overall response rates (ORR), progression-free survival (PFS), overall survival (OS) were estimated in the course of G therapy, with regard of prior treatment strategy. Treatment efficacy was assessed by PET-CT (Lugano criteria). Adverse events (AEs) were assessed by the NCI CTCAE 5.0.
Median age at G initiation was 50 years (21-83); male/female ratio, 11/17 (39/61%). Median number of previous lines of therapy before G therapy was 3 (2-8). Autologous SCT was conducted in 7 pts (25%), polatuzumab vedotin (Pola) in 7 (25%) pts. ECOG status >1 before G initiation was registered in 7 cases (25%); B symptoms, in 6 pts (21%), and bulky disease was documented in 8 (29%) pts. Median follow-up was 6 (1-15.9) months. ORR was 67% in the total group: complete response (CR), in 15 (56%) pts; partial response (PR), in 3 cases (11%); stable disease (SD), in one patient (4%); disease progression (PD), in 8 cases (30%). Eight patients died during G therapy including 5 pts (18%) who deceased due to disease progression. Eight patients died at the time of analysis, including PD in 5 cases (18%). Median OS was not reached, 6-month OS was 75.1% (95% CI, 52.0–88.2); median PFS was 10.7 months (95% CI, 5.4-NA); 6-month PFS comprised 58.8% (95% CI, 35.9-75.9). Other factors, e.g., number of previous lines of therapy, r/r clinical course, auto-HSCT, Pola therapy did not influence both OS and PFS, and development of response to G. In the course of analysis, 22 (79%) pts discontinued therapy due to PD (n=10, 36%); 5 pts (18%) had severe COVID-19 infection; 5 pts (18%) completed the scheduled therapy, and 2 pts (7%) cancelled their treatment by other reasons. The median number of G cycles was 6 (2-12). COVID-19 of any grade was revealed in 9 (32%) pts. Three pts (11%) died due to severe COVID-19. The group of patients who received Pola-BR (n=7) before G therapy was also monitored: CR was achieved in 3 pts; PR, in 2 cases, and 2 pts developed PD. Among the patients who achieved CR during Pola-BR therapy (n=3), 2 pts had relapses during the therapy, and one patient, 11 months after Pola-BR completion. The achievement of response to Pola-BR did not influence clinical response to the G therapy.
New targeted and immunotherapeutic agents significantly improve clinical prognosis in the patients with r/r B-NHL. However, curative potential of such therapy has not yet been determined, thus requiring long-term observation, as well as selection of the patients who will benefit from allo-HSCT.
Non-Hodgkin lymphoma, immunotherapy, targeted therapy, glofitamab, polatuzumab vedotin, adverse events.