High-Risk Chronic Lymphocytic Leukemia in a Young Adult Filipino Female treated with Reduced-dosage, Fixed-duration Ibrutinib and Venetoclax
Introduction/Background/Significance: Chronic lymphocytic leukemia (CLL) is a disease primarily of the elderly, however, in rare cases, it can occur among adolescent and young adults (AYA). While evidence-based guidelines are established, this include elderly with limited data among young adults. CLL in AYA is deemed high-risk disease. They experience longer survival than their older counterparts, but longevity increases their susceptibility to secondary cancers, CLL-related complications, and treatment-related adverse events. Thus, effective treatment requires careful balance of efficacy and safety.
This report emphasized a rare case of a young Filipino adult with CLL, highlighting diagnostic challenges, modified treatment regimen, and outcome. As of this writing, there are no studies or case reports on reduced-dosage and fixed-duration regimen for CLL especially in the young.
Materials and Methods/Case Presentation/Objective: A 32-year-old female presented with multiple neck masses, night sweats, weight loss, and easy fatigability. Work-up revealed anemia, 50 g/L, thrombocytopenia, 95,000 cells/mm3, and leukocytosis with lymphocytic predominance (WBC13,200 cells/mm3; ALC 10,652 cells/mm3). Cervical lymph node biopsy was compatible with small lymphocytic lymphoma (SLL). Bone marrow aspiration with biopsy revealed positivity in CD5, CD20, negative cyclin D1, CD3, CD34, and TdT. However, there were no significant expression of surface immunoglobulins (Kappa, Lambda). Due to overlapping immuno-morphologic features, and her age, B-cell acute lymphoblastic leukemia cannot be ruled out. Flow cytometry revealed bright CD200, CD23 and negative FMC7. Considering the findings, this was signed out as CLL. FISH panel for CLL revealed presence of TP53 mutation, 1.5% IGHV mutation, and ATM (11q22) mutation.
Results/Description/Main Outcome Measures: Since the patient was young, financially-constrained, and not amenable for maintenance therapy, she was given fixed-duration, reduced dosage ibrutinib with venetoclax. Her treatment regimen consisted of 28-day cycle of ibrutinib 420 mg daily for 3 months followed by dose reduction to 280 mg daily for 1 month, then maintained to 140 mg for 11 months. Venetoclax was started in the 4th cycle of therapy initially on 100mg alternate-day dosing for 2 weeks, and increased only up to a 100 mg daily dose due to recurrent anemia. Interim PET CT scan with contrast on 7th cycle of combined ibrutinib and venetoclax revealed significant decrease in the cervical lymphadenopathies, hepatomegaly, splenomegaly, and marrow heterogeneity. The treatment protocol were given for a total of 15 cycles (3-month ibrutinib lead-in followed by 12 months of reduced-dosage ibrutinib and venetoclax). Currently, the patient completed treatment, she reported significant improvement in her quality of life, and was no longer transfusion-requiring. Patient followed up continuously and was now treatment-free for 1 year, on complete remission. She was being monitored every 3 months, including CBC, and serum chemistry. She was already able to go back to her work.
Conclusions: CLL primarily affects the elderly and is extremely rare in young adults, thus, requiring thorough investigation, and presenting distinct challenges. Significant considerations include appropriate dosage adjustments while gearing towards balancing safety and efficacy, maximizing outcomes, and enhancing quality of life. Fixed-duration, reduced dosage ibrutinib and venetoclax regimen appears promising as a safe and effective treatment option for CLL patients in the AYA group especially in a resource-constrained setting.
