PolaR-ICE Effective as Second-line Treatment in DLBCL, Bridge to Autologous Stem Cell Transplant

Adding polatuzumab vedotin (polatu-zumab, Polivy) to rituximab-based salvage therapy produced strong responses and allowed 61% of patients who had failed their first treatment for diffuse large B-cell lymphomas (DLBCL) to successfully bridge to autologous stem cell transplant (ASCT), according to a phase 2 study (NCT04665765).¹

Results from 41 patients, presented during the 64th American Society of Hematology Annual Meeting and Exposition, could offer an effective option for those with relapsed or refractory DLBCL, even as chimeric antigen receptor (CAR) T-cell therapy becomes standard of care for many patients.

Alex F. Herrera, MD, a hematologist/oncologist who is associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California, presented the findings for a combination called PolaR-ICE (polatuzumab, rituximab, ifosfamide, carboplatin, and etoposide). Polatuzumab, an antibody-drug conjugate that targets CD79b, has been studied with classic chemotherapy combinations in transplant-eligible DLBCL.² It is approved for use after 2 prior therapies in the United States and as a first-line therapy in Europe.

As Herrera and some commenters noted, the data being presented were gathered before results for the ZUMA-7 (NCT03391466) and TRANSFORM (NCT03575351) studies led to approval of CAR T-cell therapy in second-line treatment for DLBCL. And yet, Herrera said, many patients who receive CAR T-cell therapy in the second line still relapse.

CAR T-cell therapy “is not necessarily the standard if they’re transplant eligible,” he said. “So, I think there’s still a role to consider studying this regimen further.”

In concluding remarks, Herrera noted the 61% of patients who proceeded to ASCT after PolaR-ICE is larger than the 36% of patients who proceeded to ASCT in the standard-of-care arm in ZUMA-7 (studying axicabtagene ciloleucel)³ or the 47% who received ASCT in the TRANSFORM trial (studying lisocabtagene maraleucel).⁴

When asked whether PolaR-ICE could even be a bridging therapy for CAR T-cell therapy, Herrera said, “I think that’s a great question.”

METHODS. Herrera outlined the study protocol, which called for eligible patients to receive 2 cycles of PolaR-ICE for 2 cycles every 3 weeks with granulocyte colony-stimulating factor, followed by PET-CT. Patients with complete response (CR) proceeded to ASCT or could receive a third cycle of PolaR-ICE at the investigator’s discretion. Patients with partial response (PR) also received a third cycle.

Following ASCT, patients who recovered from toxicities could receive 3 to 4 cycles of polatuzumab consolidation. According to the abstract, a 2-stage design was used with 20 patients enrolled (including lead-in); because 8 CRs were seen, a total of 40 patients were enrolled. Safety and CR were coprimary end points; overall response rate (ORR), progression-free survival (PFS), and overall survival were secondary end points.

RESULTS. Of the 41 patients enrolled, 37 were evaluable for response; 1 died prior to assessment, and 1 was unevaluable and replaced. One patient had clinical progressive disease (PD) and was included in ORR as PD, and 1 patient is pending evaluation. Forty patients have toxicity data available.

Twenty-two patients have received 3 cycles of PolaR-ICE; 16 were treated with 2 cycles, and 2 were treated with 1 cycle. Among 37 evaluable patients plus 1 with PD, 35 had objective response after 2 cycles of PolaR-ICE for an ORR of 92%; 21 (55%) had a CR, 14 (37%) had a PR, 1 had stable disease, and 2 had PD. Overall, the ORR after salvage for PolaR-ICE was 89% with a CR rate of 61%, after 1 patient with PR converted to PD, and 2 with PR converted to CR following a third cycle of treatment.

Thus far, 22 patients have received ASCT and 13 patients reached consolidation polatuzumab. Median follow-up time in survivors is 6.6 months; although Herrera said early data show PFS favors patients whose DLBCL relapsed after first-line treatment, longer follow-up is needed. PFS curves are in the 70% range for the patients who received ASCT, but Herrera cautioned the audience “to pause before drawing too many conclusions.”

The most common treatment-related adverse events (TRAEs) were anemia (78%), nausea (70%), thrombocytopenia (70%), leukopenia (50%), fatigue (48%), and neutropenia (48%). Grade 3 or higher TRAEs were anemia (43%), thrombocytopenia (43%), and neutropenia (43%)

References
1. 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 lympho- ma. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 442. https://ash.confex.com/ash/2022/webprogram/Paper165699.html

2. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304

3. Locke FL, Miklos DB, Jacobson CA, et al; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

4. Kamdar M, Solomon SR, Arnason J, et al; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6