Leukemia/Lymphoma/Hematologic

PD 08 - Hematologic 1 - Poster Discussion

1070 - High Dose Methotrexate Based Chemotherapy and Response Adapted Whole Brain Radiation Therapy in Primary CNS Lymphoma

Monday, October 22
4:57 PM - 5:03 PM
Location: Room 217 A/B

High Dose Methotrexate Based Chemotherapy and Response Adapted Whole Brain Radiation Therapy in Primary CNS Lymphoma
A. Biswas, N. Adhikari, A. Gogia, R. Sahoo, A. Garg, M. Sharma, S. Bhasker, V. Sreenivas, L. Kumar, and S. Chander; All India Institute of Medical Sciences, New Delhi, India

Purpose/Objective(s): We intended to assess the feasibility of response adapted whole brain radiation therapy(WBRT) after high dose methotrexate(HDMTX) based chemotherapy in patients of primary CNS lymphoma(PCNSL).

Materials/Methods: We enrolled 24 patients of PCNSL (age 18-80 years, ECOG PS 0-3, HIV seronegative, biopsy proven PCNSL, no significant end organ dysfunction) from 2015-17 in a phase II trial. The patients underwent 5 two-weekly cycles of MPV chemotherapy-methotrexate 3.5 g/m2 IV D1, vincristine 1.4 mg/m2 IV D1 & procarbazine 100 mg/m2 P.O. D1-7(in odd number cycles). Rituximab 375 mg/m2 IV D1 q2weeks was added in 16 patients as per their preference & affordability. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks. Patients with partial response(PR), stable or progressive disease(SD/PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter 2 cycles of consolidation chemotherapy with cytarabine 3 g/m2/day, IV D1 & D2 were given 1 month apart. Primary endpoints of the study were assessment of response rate & PFS. The secondary endpoints of the study were assessment of OS & toxicity profile.

Results: The median age at diagnosis was 50 years & the male:female ratio was 15:9.The ECOG PS was 3,2 & 1 in 15,5 & 4 patients respectively. Out of 20 patients who completed induction chemotherapy,10(50%) achieved CR, 9(45%) had PR & 1 had PD. 2 patients on RMPV regimen died due to sepsis. Induction chemotherapy related grade 3/4 toxicities were anemia in 2, neutropenia in 9(37.5%) & thrombocytopenia in 1 patient. 9 patients received reduced dose & 10 received standard dose WBRT. No RT related grade 3/4 toxicity was reported. Consolidation chemotherapy with cytarabine was given in 16(66.67%) patients. After a median follow-up period of 15.05 months, 5 patients had PD & 11 patients died, causes being PD in 2, sepsis in 2, unknown(PD/toxicity) in 4 & non-cancer related in 3 patients. The estimated median OS was 24.2 months. The median PFS had not been reached. The actuarial rates of 2 year PFS & OS were 61.8% & 54.8% respectively. 4 patients in reduced dose WBRT arm had recurrence & 2 of them died of PD, whereas there was no recurrence or cancer related death in standard dose WBRT arm. On univariate analysis of OS, use of RT(p<0.0001), consolidation Ara-C(p=0.013), MVP(vs RMVP) regimen(p=0.019) & no chemotherapy interruption(p=0.03), negative CSF cytology(p=0.003) led to significantly improved outcome. On multivariate analysis of OS, CSF cytology(p=0.026), chemotherapy interruption(p=0.03) & chemotherapy regimen(p=0.015) retained prognostic significance. On univariate analysis of PFS, age≤60 years & use of standard dose WBRT(45 Gy) led to significantly improved outcome(p value=0.004 & 0.04 respectively).

Conclusion: In patients with newly diagnosed PCNSL, reduced dose WBRT after complete response to HDMTX based chemotherapy may lead to sub-optimal clinical outcome due to higher risk of recurrence, progression & early death.

Author Disclosure: A. Biswas: None. N. Adhikari: None. A. Gogia: None. A. Garg: None. S. Bhasker: None. V. Sreenivas: None.

Ahitagni Biswas, MD, DNB, ECMO, FRCR

Disclosure:
No relationships to disclose.

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