Lenalidomide With Obinutuzumab Found Safe, Highly Active in Patients With Non-Hodgkin Lymphoma

Oral lenalidomide with obinutuzumab was found to be highly active and safe in patients with relapsed and refractory indolent B cell non-Hodgkin lymphomas (NHL) and was associated with prolonged remission duration, according to results of a study published in eClinicalMedicine.¹

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NHLs are comprised of slowly progressing malignancies, with follicular lymphoma (FL), marginal zone lymphoma (MZL), and small lymphocytic lymphoma (SLL) being possible outcomes. There is no established standard of care for these lymphomas; a common approach is to pursue multiple lines of chemoimmunotherapy, but this could inadvertently result in increased morbidity.¹

Novel, well-tolerated approaches are necessary to bettering outcomes among patients. Given this, the investigators sought to assess the effectiveness of immunomodulator (IMiD) drug lenalidomide combined with anti-CD20 antibody obinutuzumab in patients with relapsed and refractory indolent B-cell lymphoma.¹

In phase 1 of the trial, the primary objective was to determine the maximum tolerated dose (MTD) of lenalidomide in combination with obinutuzumab, which would be used for further evaluation in phase 2. Objectives of phase 2 were to evaluate the safety and overall response (ORR), in addition to time to progression (TTP), progression-free survival (PFS) and overall survival (OS).¹

Nine patients were enrolled in phase 1, while 57 patients were enrolled in phase 2. A lenalidomide dose of 20 mg in combination with obinutuzumab was established as the recommended dose for phase 2.¹

In phase 2, 60 patients were evaluated for activity, where 51 patients (85%) had FL, 5 patients (8%) had SLL and 4 patients (7%) had MZL. Sixty-four (97%) of 66 patients completed 6 cycles of induction therapy.¹

ORR at the end of 6 cycles of combination therapy was 90% (95% CI: 79-96) with a complete response of 33% (95% CI: 22-47), which met the primary objective. At a median follow-up of 41.7 months (range: 16.8-71.1 months), the secondary objectives of median PFS, TTP, and OS were not reached.¹

Serious adverse events were reported in 18 (27%) of the 66 patients, with the most common being lung infections (n = 5; 8%), sepsis (n = 3, 5%), fever (n =2; 3%), and sinus bradycardia (n = 2; 3%). Secondary primary malignancies were only observed in 3 patients.¹

The AUGMENT trial, conducted by Leonard et al., is typically accepted as the standard evaluating treatment in relapsed FL. This acceptance is based on the presence of a placebo-controlled arm, the regimen being deemed safe, well-tolerated, and highly active, and a median PFS reported of 39.4 months.²

Furthermore, the AUGMENT trial was enriched for patients sensitive to rituximab, and 45% experienced progression of disease within 24 months. Despite this observation, the investigators of the current study observed that the median PFS was not reached at the follow-up of 41.7 months.²

The study authors write that this supports an approach favoring lenalidomide and obinutuzumab at the first relapse of FL.^1,2

In the GALEN trial, the investigators used extended duration lenalidomide for 18 months with 20 mg for 6 months, followed by 10 mg for the remaining period. This is opposed to the current trial using the same uniform dosing of 20 mg throughout the entire trial.³

Other comparisons to the GALEN trial include similar baseline characteristics, and the GALEN trial reporting more than double the rate of grade 3-to-4 neutropenia at 44%, compared to the rate in the current trial of 20%. This was attributed to the longer duration of lenalidomide used in the GALEN trial.³

“Most patients with indolent NHL will likely have several courses of therapy, therefore, we should prioritize those with fixed duration of treatment, manageable toxicity, coupled with durability of response,” the study authors concluded.¹

References

1. Gurumurthi A, Chin CK, Feng L, et al. Safety and activity of lenalidomide in combination with obinutuzmab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase ½ trial. eClinicalMedicine. 2024;74:102747. doi:10.1016/j.eclinm.2024.102747

2. Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37(14). doi:10.1200/JCO.19.00010

3. Morschhauser F, Le Gouill S, Feugier P, et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN: a multicentre, single-arm, phase 2 study. Lancet Hematol. 2019;6(8):E429-E437. doi:10.1016/S2352-3026(19)30089-4