Introduction
Chronic lymphocytic leukemia (CLL) is not as common as other types of leukemia in India. The incidence rate of CLL in India is 0.41 per 100 000 (10 times lower than that in the United States). However, the estimate of the incidental cases is 5000 per year with a prevalence of 25 000 patients (one-third that of the estimate for the United States) (Global Burden of Disease Results Tool). There is a paucity of data and very little research on CLL from the Indian subcontinent.
Methods
D.P.L. was the recipient of the ASH Visitor Training Program award for 2013-2014. As a participant in the Visitor Training Program, the author received training in the clinical management of and research on CLL patients at the Department of Leukemia, MD Anderson Cancer Center, Houston, TX.
A comprehensive CLL clinic was established at the host institute (Postgraduate Institute of Medical Education and Research), which is a referral center for 5 neighboring states, with the following capacities to date:
An established database of CLL patients.
Fluorescent in situ hybridization (FISH) for CLL prognostication.
Flow analysis for minimal residual disease (MRD).
Assessments for quality of life.
Research on clinical outcomes in CLL.
The International Workshop on CLL guidelines are followed for diagnosis, treatment, and assessment of response. A prospective registry of the consecutive CLL patients diagnosed at this center is maintained. The choice of treatment is limited by the patient’s financial status and the availability of supportive care. The time to next treatment (TTNT) was used as the best parameter for assessing response duration.
Results
A total of 409 patients were diagnosed with CLL at this center over a period of 5 years (2013-2017). A total of 70 patients were lost to follow-up. A total of 199 patients (58.7%) received treatment, and 140 patients (41.3%) remained on observation. The median age of the CLL population was 61 years, and 31.8% of patients were age 55 years or younger. Patient fitness, as determined by a Cumulative Illness Rating Scale score of ≥3, was poor in 43.3% of patients. More than 40% (42.6% Rai stage III to IV, 40.8% Binet stage C) of the patients had advanced-stage CLL. β2-microglobulin was elevated in 53.7% of patients. FISH for prognostication was available for 40.3% of the patients. Del(13q) was the most common cytogenetic abnormality (36.9%) followed by del(17p) in 16.4% of patients. The incidence of autoimmune cytopenias was higher in our population (22.7%) with autoimmune hemolytic anemia being the most common (11%).
A bendamustine-rituximab regimen was used as first-line therapy in 31.6% of patients, and chlorambucil was used in 52.2% of patients. The overall response rates (ORRs) were 91% and 73.9%, respectively. With a median follow-up of 32 months, the TTNT was not reached (NR) with bendamustine-rituximab and was 33 months with chlorambucil (P = .001). The bendamustine-rituximab and rituximab-chlorambucil regimens were effective, even when used as second-line therapy. With an ORR of 88%, the TTNT was 42 months and NR, respectively (P = .2). Only 10% of the patients are receiving the novel agent ibrutinib because of cost constraints.
The CLL clinic has ongoing studies on MRD analysis using 8-color flow cytometry, a randomized controlled study on lenalidomide maintenance in CLL, and immune cell subset analysis in CLL. The quality-of-life assessment is part of the ongoing studies. The clinic is in the process of beginning routine testing for IGHV and TP53 mutations as predictive markers.
Discussion
The presentation of CLL in patients from India is different from that of patients in the West. The age of onset is up to a decade earlier, more patients are younger, and more patients have poor performance status. More patients have adverse prognostic markers at presentation. Bendamustine-rituximab is an acceptable first-line option in patients with poor supportive care, with outcomes that are comparable to those in clinical trials. Chlorambucil monotherapy, which has largely been abandoned by most western countries, is a valid option in resource-poor settings. It has a respectable TTNT compared with data reported in clinical trials. Re-treatment with bendamustine- and chlorambucil-based treatments can offer the same TTNT benefit as first-line therapy in a subgroup of patients.
Conclusion
Establishment of a comprehensive clinic for CLL at this academic center has led to observations that have an impact on patient care. The clinic aims to find cost-effective solutions in resource-limited settings for the diagnosis, prognosis, and treatment of CLL patients in the community.
Authorship
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Deepesh P. Lad, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India; e-mail: deepesh.lad12@gmail.com
