Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient Program

Mohan B Agarwal; Dinesh Bhurani; Chirag Shah; Nitin Sood; Manish Singhal; Anil Kamat; Subash Chezhian; Suryaprakash Mishra; Dinesh Nagrale

doi:10.4103/ijmpo.ijmpo_43_17

Indian Journal of Medical and Paediatric Oncology, Table of Contents

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2017; 38(04): 508-515
DOI: 10.4103/ijmpo.ijmpo_43_17

Original Article

Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient Program

Mohan B Agarwal

Department of Haematology, Bombay Hospital and Medical Research Centre, Mumbai, India

,

Dinesh Bhurani

Department of Hemato-Oncology and Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India

,

Chirag Shah

Department of Medical Oncology and Haematology, Apollo Hospitals International, Ahmedabad, Gujarat, India

,

Nitin Sood

Department of Medical Oncology and Haematology, Medanta-The Medicity, Gurgaon, Haryana, India

,

Manish Singhal

Departmemt of Medical Oncology, Indraprastha Apollo Hospitals, New Delhi, India

,

Anil Kamat

Departmemt of Oncology and Haematology, Jupiter Hospital, Thane, Maharashtra, India

,

Subash Chezhian

Department of Haematology, Haemato-oncology and Bone Marrow Transplant, MIOT Hospitals, Chennai, Tamil Nadu, India

,

Suryaprakash Mishra

Medical Affairs, Janssen , Mumbai, India

,

Dinesh Nagrale

Medical Affairs, Janssen , Mumbai, India

› Author Affiliations

Abstract

PDF Download

Abstract

Context: This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52–60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies. Patients received once-daily dose of ibrutinib (420 mg: CLL, 560 mg: MCL). Results: In CLL patients, the median time to response was 3 months (range, 0.5–7) and five of six patients had partial response (PR) whereas one achievedcomplete response (CR). Median time on treatment was 11.5 months (range, 8–14); five patients continued treatment and one was recommended stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin level improved from 9.8 g/dL (7.2–11) at baseline to 12.0 g/dL (9.5–13.2) and median (range) platelet count improved from 150,000 cells/μL (21,000–195,000) at baseline to 190,350 cells/μL (130,000–394,000) at the time of analysis (July 2016). Most adverse events (AEs) reported were infections (n = 2). No Grade 3-4 or serious AEs, dose reductions, or treatment discontinuation due to AEs were reported. Conclusions: In this first real-world experience in Indian patients, ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL (with/without del17p) and MCL. Safety results were consistent with the current known profile of ibrutinib.

Keywords

B-cell malignancies - Bruton's tyrosine kinase inhibitor - efficacy - ibrutinib - Indian - safety

PDF (661 kb)

References

References
1 Ho AK, Hill S, Preobrazhensky SN, Miller ME, Chen Z, Bahler DW, et al. Small B-cell neoplasms with typical mantle cell lymphoma immunophenotypes often include chronic lymphocytic leukemias. Am J Clin Pathol 2009;131:27-32.
2 Eichhorst B, Dreyling M, Robak T, Montserrat E, Hallek M, ESMO Guidelines Working Group, et al. Chronic lymphocytic leukemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011;22 Suppl 6:vi50-4.
3 McKay P, Leach M, Jackson R, Cook G, Rule S, British Committee for Standards in Haematology, et al. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol 2012;159:405-26.
4 Sellner L, Denzinger S, Dietrich S, Glimm H, Merkel O, Dreger P, et al. What do we do with chronic lymphocytic leukemia with 17p deletion? Curr Hematol Malig Rep 2013;8:81-90.
5 Hoeller S, Zhou Y, Kanagal-Shamanna R, Xu-Monette ZY, Hoehn D, Bihl M, et al. Composite mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: A clinicopathologic and molecular study. Hum Pathol 2013;44:110-21.
6 Herrmann A, Hoster E, Zwingers T, Brittinger G, Engelhard M, Meusers P, et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol 2009;27:511-8.
7 Cheng S, Ma J, Guo A, Lu P, Leonard JP, Coleman M, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia 2014;28:649-57.
8 Jares P, Colomer D, Campo E. Molecular pathogenesis of mantle cell lymphoma. J Clin Invest 2012;122:3416-23.
9 Bhatt V, Alejandro L, Michael A, Ganetsky A. The promising impact of ibrutinib, a bruton's tyrosine kinase inhibitor, for the management of lymphoid malignancies. Pharmacotherapy 2014;34:303-14.
10 Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 2011;117:6287-96.
11 Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood 2012;120:1175-84.
12 Winer ES, Ingham RR, Castillo JJ. PCI-32765: A novel bruton's tyrosine kinase inhibitor for the treatment of lymphoid malignancies. Expert Opin Investig Drugs 2012;21:355-61.
13 Imbruvica (Ibrutinib) Capsules: Highlights of Prescribing Information; 2014. Available from: https://www.imbruvica.com/prescribing-information. [Last accessed on 2017 Jan 18].
14 Cameron F, Sanford M. Ibrutinib:First global approval. Drugs 2014;74:263-71.
15 Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: A systematic analysis for the global burden of disease study 2013. Lancet 2015;386:743-800.
16 O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: An open-label, multicentre, phase 1b/2 trial. Lancet Oncol 2014;15:48-58.
17 Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013;369:507-16.
18 Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014;371:213-23.
19 Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: An international, randomised, open-label, phase 3 study. Lancet 2016;387:770-8.
20 Rule S, Dreyling M, Hess G, Auer R, Kahl B, Cavazos N, et al. Overall Survival Outcomes in Patients with Mantle-Cell Lymphoma (MCL) Treated with Ibrutinib in a Pooled Analysis of 370 Patients from 3 International Open-Label Studies. Available from: https://learningcenter.ehaweb.org/eha/2016/21st/135194/simon.rule.overall.survival.outcomes.in.patients.with.mantle-cell.lymphoma.html?f=m3. [Last accessed on 2016 Aug 25].
21 Hillmen P, O'Brien SM, Byrd JC, Coutre S, Brown JR, Barr PM, et al. Outcomes with single-agent ibrutinib by prior line of therapy and following ibrutinib discontinuation in patients with cll: analyses from phase 3 studies. Available from: https://learningcenter.ehaweb.org/eha/2016/21st/133484/peter.hillmen.outcomes.with.single-agent.ibrutinib.by.prior.line.of.therapy.html?f=m3e968. [Last accessed on 2016 Aug 25].
22 Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med 2015;373:2425-37.
23 Patil S. Early access programs: Benefits, challenges, and key considerations for successful implementation. Perspect Clin Res 2016;7:4-8.
24 Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia Updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446-56.
25 Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-86.
26 National Institutes of Health. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE); Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010). 2010. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. [Last accessed on 2016 Aug 18].
27 Byrd JC, Furman RR, Coutre SE, Burger JA, Blum KA, Coleman M, et al. Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015;125:2497-506.
28 Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: A phase 2, single-arm trial. Lancet Oncol 2015;16:169-76.
29 Kim ES, Dhillon S. Ibrutinib: A review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Drugs 2015;75:769-76.
30 de Claro RA, McGinn KM, Verdun N, Lee SL, Chiu HJ, Saber H, et al. FDA approval: Ibrutinib for patients with previously treated mantle cell lymphoma and previously treated chronic lymphocytic leukemia. Clin Cancer Res 2015;21:3586-90.
31 Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013;369:32-42.
32 Winqvist M, Asklid A, Andersson PO, Karlsson K, Karlsson C, Lauri B, et al. Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: Data from 95 consecutive patients treated in acompassionate use program. A study from the swedish chronic lymphocytic leukemia group. Haematologica 2016;101:1573-80.
33 Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, Rosin NY, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: A single-arm, phase 2 study. Lancet Oncol 2014;15:1090-9.
34 Stephens DM, Ruppert AS, Jones JA, Woyach J, Maddocks K, Jaglowski SM, et al. Impact of targeted therapy on outcome of chronic lymphocytic leukemia patients with relapsed del(17p13.1) karyotype at a single center. Leukemia 2014;28:1365-8.
35 Abrahamsson A, Albertsson-Lindblad A, Brown PN, Baumgartner-Wennerholm S, Pedersen LM, D'Amore F, et al. Real world data on primary treatment for mantle cell lymphoma: A Nordic lymphoma group observational study. Blood 2014;124:1288-95.
36 Ellin F, Landström J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: A study from the Swedish Lymphoma Registry. Blood 2014;124:1570-7.