ABSTRACT
Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Transplantation , Carboplatin/administration & dosage , Carboplatin/adverse effects , Dose-Response Relationship, Drug , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Lenalidomide , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Recurrence , Rituximab , Salvage Therapy/adverse effects , Salvage Therapy/methods , Thalidomide/administration & dosage , Thalidomide/adverse effects , Thalidomide/analogs & derivatives , Treatment OutcomeABSTRACT
Introduction: Marginal zone lymphoma (MZL) accounts for approximately 10% of all cases of non-Hodgkin lymphoma and includes 3 clinically distinct subtypes: extranodal (MALT), splenic (SMZL), and nodal (NMZL). Though commonly grouped in trials of iNHL the clinical behavior, molecular features, and response to therapy of MZL is distinct from other iNHL subtypes and varies among MZL subtypes.Areas covered: This review focuses on the contemporary management of NMZL and SMZL. Treatment with monoclonal antibodies, chemoimmunotherapy, BTK inhibitors, PI3K/mTOR inhibitors, Bcl2 inhibitors, lenalidomide, and CAR-T cell therapy will be covered.Expert opinion: In the era of targeted medicine, the need to develop MZL specific clinicogenetic models with prognostic and predictive value in both the frontline and relapsed/refractory setting is becoming increasingly apparent. Due to the relative rarity of each MZL subtype, the use of novel trial design with correlative studies is imperative to advance the field.