Among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), second-line treatment with polatuzumab vedotin combined with rituximab, ifosfamide, carboplatin, and etoposide (RICE) yields a high overall response rate (ORR) with a majority of patients experiencing a complete response (CR), according to findings from a phase 2 trial presented at the 64^th American Society of Hematology (ASH) Annual Meeting & Exposition. 

“Polatuzumab vedotin is an antibody-drug conjugate directed against CD79b that is safe and effective when combined with chemotherapy in frontline and relapsed, transplant-ineligible DLBCL,” explained Alex F. Herrera, MD, City of Hope, Duarte, CA, during his presentation. 

This multicenter, phase 2 trial aimed to evaluate the safety and efficacy of polatuzumab vedotin plus RICE in the second-line treatment of patients with relapsed/refractory DLBCL. 

The trial enrolled 41 patients with transplant-eligible relapsed/refractory DLBCL following frontline treatment with a CD20-directed anthracycline-based chemoimmunotherapy. Patients received polatuzumab vedotin 1.8 mg/kg on day 1, rituximab 375 mg/m² on day 1, etoposide 100 mg/m² on days 1 to 3, carboplatin AUC 5 on day 2, ifosfamide 5000 mg/m2 on day 2 or divided between day 1 to 3 every 21 days for 2 cycles followed by PET-CT. 

Patients who experienced a CR were eligible to proceed to autologous hematopoietic stem cell transplant (autoHSCT) or to receive a third cycle of polatuzumab vedotin plus RICE, per investigator’s decision. Patients who experienced a partial response (PR) received a third cycle of polatuzumab vedotin plus RICE. Patients who received autoHSCT and recovered from toxicities were eligible to receive consolidation therapy with polatuzumab vedotin. 

The coprimary end points of the trial were safety and CR rate. Secondary end points included ORR, progression-free survival (PFS), and overall survival (OS). 

Of the 41 patients enrolled, 37 were evaluable for response at the time of this analysis. There was 1 patient who experienced clinical progressive disease (PD) and was also counted in the ORR assessment. Toxicity data was available for 40 patients, including 22 patients who received 3 cycles of polatuzumab vedotin plus RICE, 16 patients who received 2 cycles to date, and 2 patients who received 1 cycle to date.

Of the 38 patients included in the response assessment, 35 experienced an objective response after 2 cycles of polatuzumab vedotin plus RICE (ORR, 92%), 21 (55%) experienced a CR, 14 (37%) experienced a PR, 1 patient had stable disease, and 2 patients had PD. The ORR at the end of salvage therapy was 89% and CR rate was 61%. To date, 21 patients proceeded to autoHSCT and 13 patients received consolidation therapy with polatuzumab vedotin.   

The most common treatment-related adverse events (AEs) deemed related to polatuzumab vedotin plus RICE were anemia (78%), nausea (70%), thrombocytopenia (70%), leukopenia (50%), fatigue (48%), neutropenia (48%), lymphopenia (38%), constipation (35%), hypertension (30%), and hypophosphatemia (28%). The most common treatment-related AEs of grade ≥3 were anemia (43%), thrombocytopenia (43%), neutropenia (43%). Researchers noted that no other non-hematologic treatment-related AE occurred in more than 2 (5%) patients.

Polatuzumab dose reduction due to grade 4 cytopenia and grade 2 nausea was reported for 1 patient. Grade ≥3 infection/febrile neutropenia/sepsis occurred in 3 (8%) patients. There was 1 patient who died dur to treatment-related sepsis. Grade 1 and grade 2 peripheral neuropathy occurred in 9 patients and 1 patient, respectively.

In conclusion, authors noted that “[polatuzumab vedotin plus RICE] produced a high ORR with CR in a majority of patients and the safety profile was similar to RICE, without added toxicity due to [polatuzumab vedotin].”

However, Dr Herrara did note that longer follow-up is needed to assess the durability of responses and outcomes following autoHSCT and consolidation therapy with polatuzumab vedotin.

Source:

Herrera AF, Chen L, Crombie JL, et al. Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, Louisiana, and virtual. Abstract 442.