Background
Patients with ALK+ Large B-cell Lymphoma (LBCL) generally have better OS than those with ALK-negative disease. While the optimal systemic treatment approach is not established, the following regimens have been used in the frontline setting: DA-EPOCH, CHOEP, CHOP, which are extrapolated from therapies for LBCL but without rituximab due to the lack of CD20 expression. Regarding relapsed/refractory disease, second-line platinum-based chemotherapy followed by autologous HCT for chemo sensitive disease should be considered in transplant-eligible patients, and anti CD19-CAR-T cell therapy is the current standard for early relapse (< 1 year) or primary refractory disease.
Case discussion
37-year-old Hispanic male diagnosed with stage IV ALK+ LBCL initially by staging imaging showing diffuse lymphadenopathy (LAD), and a osteobastic left iliac mass. Inguinal lymph node biopsy revealed ALK+ (t(2;17)(p23;q23)) LBCL without bone marrow or CNS involvement. Treatment was DA-EPOCH for 6 cycles, with restaging PET-CT showing progressive disease (PD). Second line treatment was DHAP, with PD after 3 cycles. Third regimen was GemOx but he developed PD after 2 cycles. Given the lack of effective therapies, his tumor was assessed for PD-L1 expression via IHC, and TPS was >50%. Based on this he started fourth line treatment with nivolumab, which led to a complete response (CR) after 6 months of therapy. Patient declinec evaluation for allogeneic transplant. After 3 years of nivolumab he developed nephrotic syndrome attributed to immunotherapy and treatmet was discontinued with resolution of this immune-related adverse effect (irAE). He continues to be in CR 3 years and 6 months after stopping nivolumab.
Conclusion
The patient underwent multiple lines of salvage chemotherapy, and ultimately immunotherapy in pursuit of disease control. The decision-making process regarding the selection and sequencing of these therapies is complex and requires consideration of factors such as disease aggressiveness, treatment response, and patient tolerance. Immunotherapy can be an option in patients with relapsed/refractory ALK+ LBCL.
