Single‐agent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differences

Abstract

SummaryWe present data from a phase II study investigating a novel treatment strategy for relapsed/refractory mantle cell lymphoma (MCL). Twenty-six patients received lenalidomide 25 mg/d (days 1-21 of a 28-d cycle) for up to 6 cycles followed by low-dose maintenance lenalidomide (15 mg) in responding patients. Eight patients achieved complete or partial response to give an overall response rate of 31% with median response duration of 22Á2 months [95% confidence interval (CI) 0Á0-53Á6] and median progression-free survival (PFS) of 3Á9 months (95% CI 0Á0-11Á1). An additional six patients (23%) achieved stable disease. Eleven patients received maintenance with median PFS of 14Á6 months (95% CI 7Á3-21Á9). Correlative studies showed that peripheral T and Natural Killer (NK) cells increased in responding patients by 40-60% over the first 6 cycles with an initial dip in NK cells suggestive of tumour infiltration. Peripheral regulatory T cells were increased in MCL patients (P = 0Á001) and expanded further following lenalidomide. Sequential plasma analysis showed increased IL12 p40 and IL7 alongside decreased MMP9, IL10, and adiponectin. Finally, a significant correlation (P = 0Á02) between gender and response suggested that female MCL patients were more sensitive to lenalidomide than males. In summary, we confirm the activity, safety and immunomodulatory properties of lenalidomide in MCL and highlight its potential as a low-dose maintenance agent.

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas

“…Responses to rituximab in patients with apparent progression of disease on lenalidomide alone were also observed. Finally, our ORR to single-agent lenalidomide, which was assessed at 2 months, is similar to the reported results for lenalidomide monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma and MCL (10,(22)(23)(24)(25)(26).…”

The current therapeutic scenario for relapsed mantle cell lymphoma

“…This immunomodulatory compound showed high antilymphoma activity in several other studies [39][40][41]. The ORR were around 30-50%, with promising CR rates up to 20% and PFS generally around 6-9 months.…”

Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities

“…26 Eve et al treated 26 relapsed/ refractory MCL cases with maintenance lenalidomide in responding patients to lenalidomide induction (Table 1). 29 In NHL-003, 57 relapsed/refractory MCL patients had an ORR of 42%. 47 Collectively, adverse effects (AEs) were primarily hematologic, with 5% of patients having thromboembolic events.…”

“…Clinical studies have examined potential biomarkers of lenalidomide efficacy, 28,29,34 and pivotal studies are ongoing in distinct NHL subsets (eg, non-GC DLBCL). In relapsed/refractory MCL, Zaja et al showed that microvessel density, macrophage, and NK cell counts were altered with lenalidomide, 28 and Ki67 is being studied as a biomarker.…”