Lenalidomide plus obinutuzumab effective in relapsed low-grade lymphoma
Click Here to Manage Email Alerts
ORLANDO — Combining lenalidomide with obinutuzumab in relapsed indolent lymphoma produced high overall response even in refractory patients and those who failed multiple lines of treatment, according to a presenter at the ASH Annual Meeting and Exposition.
“The combination of lenalidomide and obinutuzumab is very active with high response rates in low-grade relapsed lymphoma and importantly we saw very high response rates in three subsets: patients who were rituximab refractory, patients who had progressed within 2 years and patients who were in their third line of therapy,” Nathan H. Fowler, MD, of The University of Texas MD Anderson Cancer Center said during his presentation.
Fowler presented data from a phase 1/2 study in which dose escalation of lenalidomide led into treatment with the combination of lenalidomide (Revlimid, Celgene) with obinutuzumab (Gazyva, Genentech). The study objectives were to determine the maximum tolerated dose of the combination and overall response rate efficacy with secondary objectives of partial and complete response, progression free survival, overall survival and effect on tumor and immune microenvironment.
The study focused on the first six cycles of the combination treatment and offered continuation through 12 cycles total. Fowler reported data on 66 patients.
Median time to response was 3 months and 23 patients remain on therapy, with the vast majority in the maintenance phase, Fowler said.
Fowler reported that patients with follicular lymphoma (n = 57) had 100% overall response and 75% had a complete response. In the patients with marginal or SLL (n = 9), 88% had an overall response and 44% had a complete response, he said.
“Patients that were rituximab refractory, although only 16 patients, all of them responded to obinutuzumab plus lenalidomide with a CR rate of 63%,” Fowler said. “Looking at patients in their third line of therapy, which is where most of the recently approved of the drugs are, we saw an OR of 97% with a CR rate of 68%.”
Additionally, patients that progressed within 2 years of their first-line therapy (n = 27) showed a 96% OR rate and 66% CR rate.
“You can see a trend that regardless of these different populations, the OR rate and CR rate are fairly similar,” he said. “To me, one of the most impressive aspects of this data is the rituximab refractoriness. We know that patients who are rituximab refractory if you would use rituximab or even obinutuzumab as a single agent, the response rates are much, much lower – you’re looking at 50% or less. I do think that – especially in patients who are failing rituximab – it appears that lenalidomide adds to obinutuzumab which in other prior studies we have not seen any response like this.”
Though current follow-up is only at 17.7 months, Fowler showed projected survival rates overall and within the subsets. For all patients, the researchers project a 73% PFS (95% CI, 58-83%) and an OS of 94% (95% CI, 77-98%).
For marginal zone/SLL, PFS projected at 65%. For follicular lymphoma, PFS projected at 74%. For those patients on at least their third therapy, PFS was 64%. And patients who completed six or less cycles of the combination treatment were projected to have 72% PFS while those who completed more than 6 cycles were projected to have a PFS of 78%.
Fowler showed safety results in which grade 3 or higher hematologic toxicities presented as 2% with anemia, 9% with neutropenia and 2% with thrombocytopenia. Non-hematologic adverse events were likely to be infection (14%), rash, cough, constipation and diarrhea.
“The toxicity profile was very similar to what was reported in several trials with lenalidomide and rituximab,” Fowler said. “We are working on correlative trials that will hopefully be able to predict patients who progress early but I will freely admit that this is a phase 2 trial and larger phase 3 trials are needed to truly understand if this regimen is better than R squared in the relapse setting.” – by Katrina Altersitz
Reference:
Fowler N, et al. Abstract 348. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando, Florida.
Disclosures: Fowler reports serving on advisory committees and receiving research funding from AbbVie, Celgene, Janssen, Novartis, Roche and TG Therapeutics.