Response to challenges in defining a new standard of care in Primary CNS Lymphoma

On November 17th 2016, the Lymphoma Hub published an article on a response by Marc C. Chamberlain to the Phase I/II NRG Oncology RTOG 0227 trial by Glass et al., published in May 2016. The main concerns raised by Chamberlain and subsequently addressed by Glass et al. were:

• Myeloablative conditioning chemotherapy followed by ASCT are more frequently being suggested as alternatives to consolidation WBRT
  • Glass et al. responded by stating that in the age groups in which this disease is most common many patients would not be eligible based upon their physiology
• Mini-mental state examination is not a very sensitive method of assessing cognitive function
  • Glass et al. responded by stating that they agree, and furthermore that the goal of using this method was to determine substantial changes in cognitive function

Glass et al. concluded their response by suggesting that going forward, clinicians should recruit for modest-sized Phase II trials that should be completed quickly in order to rapidly find treatments which may significantly improve patient outcome. These treatments should then be rapidly progressed to a Phase III trial in order to maximize treatment options, given the rarity of Primary CNS Lymphoma. However, in their opinion, their trial into methotrexate, temozolomide (TMZ) with rituximab, proceeded by hyperfractionated Whole-Brain Radiotherapy (hWBRT) remains a reasonable option for future trials to assess.

References:

1. Glass J. et al. Reply to M.C. Chamberlain. Journal of Clinical Oncology. 2016 Nov; 34(33): 4057. doi: 10.1200/JCO.2016.69.6047.
2. Chamberlain M.C. Immunochemotherapy, the New Standard of Care for Primary CNS Lymphoma: However, Which One? Journal of Clinical Oncology. 2016 Oct; 34(33):4056–4057. doi: 10.1200/JCO.2016.68.9018.
3. Glass J. et al. Phase I and II Study of Induction Chemotherapy With Methotrexate, Rituximab, and Temozolomide, Followed By Whole-Brain Radiotherapy and Postirradiation Temozolomide for Primary CNS Lymphoma: NRG Oncology RTOG 0227. Journal of Clinical Oncology. 2016 May; 34(14):1620–5. doi: 10.1200/JCO.2015.64.