Data evaluating combination therapy with REVLIMID and rituximab in patients with NHL presented

Dec 9 2009

Celgene International Sàrl (NASDAQ: CELG) announced that investigational data evaluating combination therapy with REVLIMID (lenalidomide) and rituximab in patients with indolent non-Hodgkin’s lymphoma (NHL) were presented during the 51^st American Society of Hematology’s annual meeting in New Orleans, LA. The phase II investigator-initiated studies explored the potential clinical synergy of these two agents in patients with indolent NHL, which includes patients with the follicular lymphoma histologic subtype.

The first study, led by Joseph Tuscano, MD and presented by Mrinal Dutia, MD both from University of California-Davis Cancer Center, evaluated the REVLIMID plus rituximab combination in patients with relapsed/refractory indolent NHL. All 16 patients on study had received a median of three prior therapies, which included either rituximab or rituximab-containing chemotherapy regimens. In this study, the preliminary overall response rate (ORR) is 75% (12 out of 16 patients), including 31% of patients>

Most common Grade 3 or 4 adverse events included fatigue (12%), neutropaenia (18%), lymphopaenia (25%) and hyponatraemia (18%). Two cases of tumour lysis syndrome (both in patients not receiving prophylaxis) were managed by reducing the dose to 20 mg per day and employing standard prophylaxis.

The second study, led by Stephen Schuster, MD and presented by Tahamlan Ahmadi, MD, PhD both from the Abramson Cancer Center, University of Pennsylvania, assessed the effects of extended treatment with REVLIMID^® plus low-dose dexamethasone with four weekly doses of rituximab added in Cycle 3 in 24 patients with indolent B-cell or mantle cell lymphomas who are resistant to rituximab. Among 15 of 24 patients who completed five cycles of therapy by the time of the analysis, the preliminary ORR was 53%, including 33% of patients who achieved a CR. At a median follow-up of 10.9 months, 86% of patients disease had not progressed.

Among these 15 patients, the most common Grade 3 or 4 non-haematologic adverse events were hypokalemia (13%), hypophosphataemia (13%), pulmonary embolism (7%), pneumonia (20%) and hypocalcaemia (7% patients). Grade 1 tumour flare occurred in one patient with follicular lymphoma,and no cases of tumour lysis syndrome occurred.

The third study led by Felipe Samaniego, MD and presented by Nathan Fowler, MD both from the Department of Lymphoma and Myeloma, MD Anderson Cancer Center, assessed the clinical efficacy and safety of the REVLIMD and rituximab combination in front-line therapy in 30 patients with stage III or IV indolent B-cell NHL. The study reported results for the first 28 patients with NHL subtypes, which included 17 patients with follicular lymphoma, eight patients with marginal zone lymphoma, and three patients with small lymphocytic lymphoma. Twenty-four patients (86%) responded to therapy including 21 patients (75%) who achieved a CR/Cru. Of note, these investigators reported that 16 of 17 patients (94%) with follicular lymphoma achieved a CR/CRu after completing six cycles of therapy.

In this study, the most common Grade 3 or 4 adverse events were rash (20%), neutropaenia (23%), and myalgia (13%) among 30 patients who were evaluated for toxicity. No patients developed tumor lysis syndrome.

Side effects associated with the REVLIMID plus rituximab combination were consistent between the studies evaluating this therapy, and not significantly different from that observed with REVLIMID alone. Tumour lysis was not observed in patients who received standard tumour lysis prophylaxis.