Triplet Staves Off Progression

The combination of polatuzumab vedotin, obinutuzumab, and lenalidomide demonstrated efficacy in a phase 1b/2 trial, according to study presenter Catherine Diefenbach, MD, of the Perlmutter Cancer Center at NYU Langone Health in New York, New York.4

The trial (ClinicalTrials.gov Identifier: NCT02600897) enrolled patients with grade 1-3A, relapsed/refractory FL. The 56 patients had a median age of 62 years (range, 32-87) at baseline, and 88% of patients had stage III/IV disease. Patients had received a median of 3 prior lines of therapy (range, 1-7), 59% had disease that was refractory to their last therapy, and 27% had progression within 24 months of diagnosis.


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The recommended phase 2 dose was polatuzumab vedotin at 1.4 mg/kg (on day 1), obinutuzumab at 1000 mg (on days 1, 8, and 15 of cycle 1 and day 1 of cycles 2-6), and lenalidomide at 20 mg (once daily on days 1-21 of each 28-day cycle). 

Patients received 6 cycles of induction. Those who responded or had stable disease after induction received maintenance with obinutuzumab (once every 2 months for 24 months) and lenalidomide (once daily on days 1-21 for 12 months).

The safety population included all 56 patients, and the median follow-up was 43.5 months. The rate of grade 3 or higher AEs was 86%, and 3 patients had a fatal AE. Most patients (77%) had an AE leading to dose interruption, and 34% had an AE leading to discontinuation.

The most common AEs were infections and infestations (75%), neutropenia (64%), thrombocytopenia (54%), diarrhea (43%), anemia (41%), infusion-related reactions (39%), pyrexia (38%), and peripheral neuropathy (29%). 

The efficacy population included 46 patients who received the recommended phase 2 dose, and the median follow-up was 43.3 months. By investigator assessment using modified Lugano criteria, the ORR was 83%, and the CR rate was 61%. By independent review, the ORR was 76%, and the CR rate was 61%.

The median PFS was not reached. The PFS rate was 83.3% at 12 months, 67.4% at 24 months, 64.6% at 36 months, and 53.4% at 48 months. The median OS was not reached.

When asked how this regimen compares with bispecific antibodies and CAR T-cell therapy, Dr Diefenbach noted that bispecific antibodies are “certainly more glamorous,” than this triplet. However, the median PFS was 20.2 months with odronextamab and was not reached after 3 years with this triplet.  

“This is obviously a highly active regimen that induces durable complete responses with drugs that people are familiar with, which combine well and play well with each other in the sandbox,” Dr Diefenbach said. “So I think there’s certainly a place for this for patients with relapsed follicular lymphoma.” 

“It’s an interesting combination,” said Dr Torka, who was not involved in this study. “All 3 drugs are already approved for different settings. The next step would be a randomized study showing this combination is better than lenalidomide plus rituximab.”

Disclosures: The Watch & Wait trial was partly supported by Roche Pharma AG. The ELARA trial was supported by Novartis. The ELM-2 trial was supported by Regeneron Pharmaceuticals. The triplet trial was supported by Hoffmann-La Roche. Dr Torka disclosed relationships with ADC Therapeutics, Epizyme, Targeted Oncology, Physician Education Review, TG Therapeutics, Lilly USA, and Genentech. Some of the study presenters and their colleagues declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of their disclosures.  

References

1. Northend M, Wilson W, Clifton-Hadley L, et al. Long term follow-up of international randomised phase 3 study of rituximab versus a watch and wait approach for patients with asymptomatic, low tumour burden follicular lymphoma shows rituximab is highly effective at delaying time to new treatment without detrimental impact following next line of therapy. Presented at ASH 2022. December 10-13, 2022. Abstract 607.

2. Dreyling M, Dickinson M, Martinez Lopez J, et al. Long-term clinical outcomes and correlative efficacy analyses in patients (pts) with relapsed/refractory follicular lymphoma (r/r FL) treated with tisagenlecleucel in the Elara trial. Presented at ASH 2022. December 10-13, 2022. Abstract 608.

3. Kim TM, Taszner M, Cho SG, et al. Odronextamab in patients with relapsed/refractory (r/r) follicular lymphoma (FL) grade 1–3a: Results from a prespecified analysis of the pivotal phase II study ELM-2. Presented at ASH 2022. December 10-13, 2022. Abstract 949.

4. Diefenbach CS, Kahl BS, Banerjee L, et al. A phase Ib/II study of polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed/refractory follicular lymphoma: Final analysis and progression-free survival update. Presented at ASH 2022. December 10-13, 2022. Abstract 951.

5. Ardeshna KM, Qian W, Smith P, et al. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: An open-label randomised phase 3 trial. Lancet Oncol. 2014;15(4):424-35. doi:10.1016/S1470-2045(14)70027-0 

6. Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: The phase 2 ELARA trial. Nat Med. 2022;28(2):325-332. doi:10.1038/s41591-021-01622-0.