acalabrutinib, relapsed, refractory, treatment-naïve, BTK inhibitor. NHL-225. Primary Central Nervous System. Lymphoma in India: A 17-year. Experience from ...
Abstracts 8
Academic Medical Center, University of Amsterdam, Amsterdam, 9
Netherlands; Institute of Hematology University of Bologna, Bologna, Italy; 10Royal Marsden Hospital, London, United Kingdom; 11Churchill Hospital, Oxford, United Kingdom;
12
University Medical Center
Utrecht Cancer Center, Utrecht, Netherlands;
13
distrian University of Athens, Athens, Greece;
14
Atul Sharma,1 Ajay Gogia,1 Atul Batra,1 Bidhu Mohanti,2 Ajay Garg,5 Mehar Sharma,4 Sanjay Thulkar,3 Sreenivas Vishnubhatla,5 Saphalta Baghmar1
National and Kapo-
1
Acerta Pharma,
Hospital, All India Institute of Medical Sciences, New Delhi, Delhi, In-
Department of Medical Oncology, Dr. B. R.A. Institute Rotary Cancer
Redwood City, California, United States; 15Acerta Pharma, Oss, Netherlands; 16Weill Cornell Medical College, New York Presbyterian
dia; 2Department of Radiation Oncology, Dr. B. R.A. Institute Rotary
Hospital, New York, New York, United States
Delhi, India; 3Department of Radiology, Dr. B. R.A. Institute Rotary
Cancer Hospital, All India Institute of Medical Sciences, New Delhi, Cancer Hospital, All India Institute of Medical Sciences, New Delhi,
Context: 2Bruton tyrosine kinase (BTK) is a clinically validated target in WM. Acalabrutinib is a highly selective, potent, covalent BTK inhibitor that we evaluated in a Phase 2 study of pts with treatmentnaive (TN) or relapsed/refractory (R/R) WM. Design: Pts with TN or R/R WM received 100 mg acalabrutinib BID (or 200 mg QD [n¼6], later switched to 100 mg BID) in 28-day cycles until progressive disease (PD) or intolerance. Main outcome measures: The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and PK. Results: One hundred six pts (14 TN and 92 R/R) were treated; median age was 69 y (range 39-90); 94% had ECOG PS 1; median serum IgM was 3615 mg/dL (range 291-9740). R/R pts had a median of 2 prior therapies (range 1-7). At a 25-mo median follow-up, 7 (50%) TN and 70 (76%) R/R pts remain on treatment. Discontinuations were primarily due to PD (TN 0 pts; R/R 9 pts), adverse events (AEs; TN 3; R/R 3), and investigator decision (TN 2; R/R 4). BTK occupancy and PK parameters were consistent with previous acalabrutinib studies. ORR was 93 [66, 100]% and 94 [86,98]% in TN and R/R patients, respectively. The 24-month rate DOR, PFS and OS were TN: 90 [47, 99]%, 90 [47, 99]% and 92 [54, 99]%; and R/R: 84 [73, 90]%, 82 [72, 88]% and 89 [80, 94]%, respectively. Common AEs (any grade) were headache (39%), diarrhea (31%), contusion (29%), and dizziness (25%). Common Gr 3/4 AEs were neutropenia (16%), pneumonia (7%), anemia, increased ALT, and hyponatremia (each 5%). Atrial fibrillation occurred in 3 pts (1 Gr 3). Bleeding events occurred in 57% of pts (commonly contusion [29%] and epistaxis [13%]); 4 events were Gr 3/4: epistaxis, hematuria, dysfunctional uterine bleeding, and retinal hemorrhage. There were 5 Gr 5 events: pneumonia, glioblastoma multiforme, esophageal carcinoma, myocardial ischemia, and intracranial hematoma. Conclusions: Acalabrutinib is a highly effective treatment for WM with durable responses and limited toxicity. Funding source: Acerta Pharma, member of AstraZeneca Group (NCT02180724). Keywords: Waldenström macroglobulinemia, acalabrutinib, relapsed, refractory, treatment-naïve, BTK inhibitor
NHL-225 Primary Central Nervous System Lymphoma in India: A 17-year Experience from AIIMS
Ranjit Sahoo ,1 Mukesh Patekar,1 Narayan Adhikari,2 Ahitagni Biswas,2 Vinod Raina,1 Lalit Kumar,1
S286
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Clinical Lymphoma, Myeloma & Leukemia September 2018
Delhi, India; 4Department of Pathology, Dr. B. R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, Delhi, India; 5Department of Radiology, All India Institute of Medical Sciences, New Delhi, Delhi, India; 6Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, Delhi, India
Context: In spite of numerous advances in the field of PCNSL, there are significant barriers with respect to managing this rare and aggressive brain neoplasm. There is no populationbased data for PCNSL in India and in such scenario a large hospital-based data may put some light. Setting: All India Institute of Medical Sciences (AIIMS) is a tertiary care center in the northern part of India. Objective: To analyze outcome of patients diagnosed with PCNSL. Design: This is a retrospective study spanning over 17 years from 2001-2017. The median duration of follow-up is 34 months. Results: Out of 99 patients, only one patient was found positive for HIV-serology. The median age was 50 years (13-70 years) with a male: female ratio of 1.91. The median duration of symptoms before diagnosis was 3.5 months (0.5-48 months). In 81.8% of patients, there were multiple intracranial lesions predominantly in the supratentorial location. Performance status of 3 or more was seen in 58.5%. The most common histology was DLBCL (97.7%). Approximately 30% of patients were not eligible for treatment because of the poor general condition. Surgical resection was performed in 45% (n¼40) due to suspicion of glioma or other brain tumor (n¼36). Most patients (n¼73) were treated with MVP+R without any pharmacokinetic monitoring of MTX with acceptable toxicity (HDMTX-related mortality of 3.9%). The median EFS and OS were 20.4 months and 31.7 months respectively. Addition of rituximab to MVP (n¼27) resulted in higher ORR (88.9% vs. 73.9%, p¼0.12), CR (81.5% vs. 56.5%, p¼0.03), 2-year EFS (57.3% vs. 40.4%, p¼0.02) and 2-year OS (61.6% vs. 53.4%, p¼0.056) as compared to MVP alone. Conclusion: This is the largest study of PCNSL from India representative of the experiences across all parts of the country. Patients were younger, immunocompetent and presented with a high-burden disease at baseline (multiple lesions, poor PS) with w30% patients being unsuitable for any curative treatment. The outcome of patients who could be treated appears comparable to the west with addition of rituximab showing a benefit. The toxicity of HDMTX without pharmacokinetic monitoring was acceptable. Keywords: Primary Central Nervous System Lymphoma, PCNSL, Retrospective, India
