Clinical Scorecard: Long-term remission observed following the cessation of ALK inhibition in patients with ALK-positive histiocytosis
At a Glance
Category
Detail
Condition
ALK-positive histiocytosis, a rare histiocytic neoplasm driven by ALK gene fusions
Key Mechanisms
Disease driven primarily by KIF5B::ALK fusions and other ALK rearrangements; targeted by ALK inhibitors
Target Population
Children and adults with ALK-positive histiocytosis, including those with neurologic and multisystemic involvement
Care Setting
Specialized oncology and hematology centers with access to molecular diagnostics and targeted therapies
Key Highlights
Universal objective response (100%) to ALK inhibitors observed in 27 patients, with 56% achieving complete response and 44% partial response.
Sustained remission after discontinuation of ALK inhibitors in 18 of 19 patients who stopped therapy, with median treatment-free remission of 1.8 years.
Adverse events were common (78%) but mostly grade 1 or 2 and manageable; grade 3 events occurred in 37%, and grade 4 events were rare.
Guideline-Based Recommendations
Diagnosis
Diagnosis based on established criteria including molecular confirmation of ALK fusions (e.g., KIF5B::ALK, DCTN1::ALK, CLTC::ALK).
Central pathology review recommended for cases with non-KIF5B::ALK fusions.
Use of imaging modalities (MRI, PET) to assess disease extent and response.
Management
Initiate ALK inhibitor therapy (alectinib preferred, followed by crizotinib, lorlatinib, or brigatinib) as first-line or subsequent therapy.
Monitor and manage adverse events; dose adjustments or therapy changes may be necessary for toxicity.
Consider elective discontinuation of ALK inhibitors in patients achieving clinical remission with sustained response.
Monitoring & Follow-up
Regular clinical and imaging assessments to evaluate treatment response and detect relapse.
Use of PET and MRI to confirm complete or partial responses.
Close follow-up after therapy cessation to monitor for disease recurrence.
Risks
Potential for relapse after ALK inhibitor discontinuation, though rare; relapse can respond to reinitiation of therapy.
Adverse events including hypercholesterolemia, anaphylaxis, and hemolytic anemia require vigilance.
Non-adherence and other medical conditions may impact treatment continuity.
Patient & Prescribing Data
27 patients (16 children, 11 adults) with ALK-positive histiocytosis, including neurologic and multisystemic disease.
Median treatment duration was 2 years; responses typically rapid (median 2 months). Therapy discontinuation feasible with sustained remission in most cases.
Clinical Best Practices
Confirm ALK fusion status molecularly before initiating targeted therapy.
Select ALK inhibitor based on patient tolerance and prior adverse events.
Monitor patients closely for adverse events and adjust therapy accordingly.
Consider treatment discontinuation in patients with sustained remission under careful observation.
Reinitiate ALK inhibitor promptly if relapse occurs after cessation.
by Paul G. Kemps, Jennifer L. Picarsic, Sébastien Héritier, Jean Donadieu, Julien Haroche, Laure Farnault, Stefania Gaspari, Dmitry A. Evseev, Daria S. Osipova, Alexander E. Druy, Milen Minkov, Susan Picton, Andreas Beilken, Robert Möhle, Miloš B. Kuzmanović, Hitomi S. Okuma, Chung W. Chow, Martin A. Campbell, Gregory S. Phillips, Yuhang Zhou, Gaurav Goyal, Ronald S. Go, Kee Kiat Yeo, Bryan A. Sisk, Joanna L. Weinstein, Patrick K. Campbell, Eli L. Diamond, Jean-François Emile
