Chemo-free regimen shows promise for follicular lymphoma
A novel, immunomodulatory, chemotherapy-free combination comprising rituximab and lenalidomide (R2) demonstrated similar efficacy with the standard rituximab plus chemotherapy (R-chemo) followed by rituximab maintenance for advanced follicular lymphoma (FL), according to data from the RELEVANCE* trial presented at EHA 2018.
After a median follow-up of 37.9 months, central and investigator reviews revealed similar rates between R2 and R-chemo arms in terms of complete response (CR) and complete response unconfirmed (CRu; 48 percent vs 53 percent; p=0.13 and 55 percent vs 58 percent; p=0.38, respectively) and duration of CR and CRu (77 percent vs 81 percent, hazard ratio [HR], 0.93 and 86 percent vs 81 percent, HR, 0.66, respectively). [EHA 2018, abstract S154]
Similar progression-free survival (PFS) rates were also observed between the R2 and R-chemo arms per central and investigator assessments (77 percent vs 78 percent, HR, 1.10; p=0.48 and 77 percent vs 78 percent, HR, 0.94; p=0.63).
The comparable findings between R2 and R-chemo in terms of CR/CRu and interim PFS underscore the potential of R2 as a first-line treatment alternative to the cytotoxic R-chemo for FL, which is usually characterized by a history of recurrent relapse that are shorter with each line of therapy, said Dr Franck Morschhauser from the Centre Hospitalier Universitaire Regional de Lille in Lille, France.
Furthermore, Morschhauser indicated that 3-year overall survival (OS) was ‘excellent’ at 94 percent for both R2 and R-chemo arms (HR, 1.16), though these findings were still immature.
Patients with high tumour burden FL (n=1,030, median age 59 years) were randomized 1:1 to receive either R2 or R-chemo for a total duration of 120 weeks (induction, second, and maintenance phases). R2 recipients received lenalidomide 20 mg which was reduced to 10 mg in the second phase if response was achieved, while R-chemo recipients received standard R-CHOP, R-B, or R-CVP** per investigator’s/patient’s choice during the induction phase. All R2 and R-chemo recipients also received rituximab 375 mg/m2/week (cycle 1 and day 1 of cycles 2–6 during the induction phase and every 8 weeks thereafter).
Overall, the results show that R2 ‘did well’, said Morschhauser, considering the high-risk population (94 percent at stage 3/4) with bulky disease (42 percent) and high-risk FLIPI*** scores (49 percent).
The two regimens had different toxicity profiles, where compared with patients on R-chemo, those on R2 had lower rates of grade 3–4 neutropenia (32 percent vs 50 percent), febrile neutropenia (2 percent vs 7 percent), infections requiring hospitalization (9 percent vs 12 percent), nausea (20 percent vs 42 percent), peripheral neuropathy (11 percent vs 22 percent), vomiting (7 percent vs 19 percent), and alopecia (1 percent vs 9 percent), but higher rates of skin toxicities (43 percent vs 24 percent), diarrhoea (37 percent vs 19 percent), tumour flare reaction (6 percent vs 0.2 percent), and grade 3–4 cutaneous reactions (7 percent vs 1 percent).
These discrepancies could have been due to a slight underreporting of adverse events in R-chemo and overreporting in the R2 regimen as most of the investigators were not used to the R2 regimen, said Morschhauser. “[Nonetheless, the results on] neutropenia, febrile neutropenia, infections, and rash were something that really stands out in terms of toxicity.”
“[Our findings are] the first demonstration of similarity [between R2 and R-chemo] … This is a clear path forward for other researches,” said Morschhauser. “We need more follow-up to see whether this will stand with time and whether there will be changes in [OS].”
Further studies will also report on quality of life, minimal residual disease, and PET# data, which will be presented in future meetings, he concluded.