Background: ALK-positive anaplastic large-cell lymphoma (ALCL) usually carries a favorable prognosis in young adults. However, refractory or multiply relapsed disease remains a major therapeutic challenge. Data supporting sequential use of next-generation ALK inhibitors in systemic ALCL are limited.
Case Presentation: A 25-year-old woman presented with inflammatory presternal skin lesions, widespread lymphadenopathy and B symptoms. Skin and lymph node biopsies confirmed ALK+, CD30+, CD3–, CD4+, CD8–, EMA+ systemic ALCL (stage IV, aaIPI=1). CHOP chemotherapy induced a complete metabolic response (CMR), followed by early relapse.
BV-GVD achieved a second CMR, consolidated with an allogeneic stem-cell transplant. Early post-transplant relapse was controlled by immunosuppression tapering and Brentuximab-Vedotin (BV). A subsequent relapse treated for 11 months with crizotinib achieved partial metabolic response and MRD negativity.
Then, over a 3-year period, multiple cutaneous, nodal, and renal relapses occurred despite vinblastine, radiotherapy, BV-GVD, and crizotinib retreatment. Brigatinib induced a durable CMR lasting 18 months. Then, a paravertebral relapse was successfully treated with BV-bendamustine, followed by BV maintenance. Then, disseminated relapse (nodal, pleuropulmonary, bone lesions) prompted initiation of lorlatinib, achieving rapid partial response and CMR at four months, sustained at nine months.
Conclusion: This case demonstrates sustained disease control through sequential ALK inhibition despite prior resistance to crizotinib. Sequential ALK inhibitors offered meaningful disease control even in the post-transplant setting, where therapeutic options are limited by cumulative toxicities. Lorlatinib achieved rapid and durable remission after multiple prior ALK inhibitors and brentuximab, suggesting its potential as an effective rescue strategy in resistant ALK+ ALCL.
