LY-07. Polatuzumab vedotin in combination with bendamustine and rituximab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: interim analysis of real life experience CIC 725
Olesya G. Smykova, Vladislav V. Markelov, Liudmila V. Fedorova, Kirill V. Lepik, Elena V. Kondakova, LiliaV. Stelmakh, Ivan S. Moiseev, Natalya B. Mikhailova, Alexander D. Kulagin
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
Correspondence:
Dr. Olesya G. Smykova, e-mail: olesya.gen@gmail.com
Summary
The outcome of relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) in patients who are not candidates for auto-SCT is dismal due to absence of therapeutic standards. Relapsed or refractory B-NHL is a heterogeneous group of lymphoproliferative malignancies with histological, cytogenetic and molecular differences, but all of them have a B-cell receptor. CD79b is a B-cell receptor component and the antibody-drug conjugate polatuzumab vedotin is an anti-CD79b antibody linked to antimitotic agent – monomethyl auristatin E. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) demonstrated efficacy in patients with r/r B-NHL.
Patients and methods
This is interim analysis of single-center study evaluates efficacy and safety of Pola-BR for the treatment of patients with aggressive r/r B-NHL. All patients received bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2 on day 1 and polatuzumab vedotin 1.8 mg/kg on day 1 of each 21-day cycle. The PET-CT scan was performed before treatment initiation and after 2, 4, 6 cycles of Pola-BR. The responses were evaluated using Lugano 2014 criteria. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
Results
A total of 32 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (n=24), primary mediastinal B-cell lymphoma (PMBCL) (n=7) and gray zone lymphoma (GZL) (n=1) were included in the analysis. All diagnoses were histologically confirmed. The median age was 42 years (range 19-69). Most of the patients 81% (n=26) had primary refractory disease. The median number of prior therapeutic lines was 3 (range 2-10). Five patients (16%) underwent autologous stem cell transplantation and four patients (13%) received anti-CD19 CAR-T cell therapy. At the start of Pola-BR treatment, the Ann Arbor stage III-IV was detected in 88% (n=28) patients, and bulky disease was in 31% (n=10) patients. Median number of Pola-BR cycles was 3 (range 2-6). Sixteen patients (50%) completed 6 cycles of Pola-BR. Fourteen patients (44%) interrupted Pola-BR treatment due to disease progression. At the median follow-up of 12 months (range 2-19), the overall response rate (ORR) in all group of patients was 57% (n=18) with 44% (n=14) of complete response (CR) and 13% (n=4) of partial response (PR). Two patients (6%) showed stabilization of the disease as best response. The ORR in patients with DLBCL was 54% (CR 41%), being 57% in the patients with PMBCL ORR, (CR 43%), and one patient with GZL achieved CR. The ORR in patients with bulky disease was 10% (CR 10%) vs ORR 79% (CR 61%) respectively in patients without bulky disease (p=0.2, p=0.05). In the patients with relapsed disease, ORR was 83% (CR 67%) vs ORR of 53% (CR 39%) in patients with primary refractory disease (p=0.4, p=0.4). Two patients (50%) with primary CAR-T cell therapy achieved CR. One-year overall survival (OS) and progression-free survival (PFS) in the entire group were 57% and 25%, respectively. Median PFS in total group was 4 months, and median OS value was not reached. OS and PFS in patients who achieved response were 81% and 45%, respectively, with median PFS of 16.8 months. OS and PFS rates were significantly higher in the patients without bulky disease 72% vs 21% (p=0.004), and 30% vs 10% (p=0.007), respectively. Seven patients who progressed or relapsed after Pola-BR received glofitamab with obinutuzumab treatment, two patients achieved CR, one had indeterminate response, one patient showed progression of the disease, and the response was not evaluated in 2 cases. During Pola-BR treatment, grade 3-4 anemia, neutropenia, and thrombocytopenia were observed in 19% (n=6), 41% (n=13) and 16% (n=5) cases, respectively. Other adverse events included neutropenic fever 6% (n=2) and maculo-papular rash 6% (n=2). There were no cases of peripheral neuropathy. Two patients with PR died due to COVID-19 infection after 2 and 4 cycles of Pola-BR.
Conclusion
Our real-life data confirms that Pola-BR has an acceptable toxicity profile, being a promising method of immunochemotherapy for patients with r/r B-NHL.
Keywords
Non-Hodgkin lymphoma, refractory, polatuzumab vedotin, bendamustine, rituximab, therapy, interim analysis.
