Myeloablative vs nonmyeloablative consolidation for primary central nervous system lymphoma: results of Alliance 51101.
Tracy T BatchelorSharmila GiriAmy S RuppertSusan M GeyerScott E SmithNimish MohileLode J SwinnenJonathan W FriedbergBrad S KahlNancy L BartlettEric D HsiBruce D ChesonNina D Wagner-JohnstonLakshmi NayakJohn P LeonardJames L RubensteinPublished in: Blood advances (2024)
Although it is evident that standard-dose whole-brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the US Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with nonmyeloablative consolidation after induction therapy for PCNSL. To our knowledge, this is the first randomized trial to be initiated that eliminates whole-brain radiotherapy as a consolidative approach in newly diagnosed PCNSL. Patients aged 18 to 75 years were randomly assigned in a 1:1 manner to induction therapy (methotrexate, temozolomide, rituximab, and cytarabine) followed by consolidation with either thiotepa plus carmustine and autologous stem cell rescue vs induction followed by nonmyeloablative, infusional etoposide plus cytarabine. The primary end point was progression-free survival (PFS). A total of 113 patients were randomized, and 108 (54 in each arm) were evaluable. More patients in the nonmyeloablative arm experienced progressive disease or death during induction (28% vs 11%; P = .05). Thirty-six patients received autologous stem cell transplant, and 34 received nonmyeloablative consolidation. The estimated 2-year PFS was higher in the myeloablative vs nonmyeloablative arm (73% vs 51%; P = .02). However, a planned secondary analysis, landmarked at start of the consolidation, revealed that the estimated 2-year PFS in those who completed consolidation therapy was not significantly different between the arms (86% vs 71%; P = .21). Both consolidative strategies yielded encouraging efficacy and similar toxicity profiles. This trial was registered at www.clininicals.gov as #NCT01511562.
Keyphrases
- hodgkin lymphoma
- newly diagnosed
- stem cell transplantation
- end stage renal disease
- stem cells
- clinical trial
- ejection fraction
- chronic kidney disease
- prognostic factors
- high dose
- peritoneal dialysis
- randomized controlled trial
- early stage
- cell therapy
- white matter
- squamous cell carcinoma
- multiple sclerosis
- radiation therapy
- low dose
- free survival
- patient reported outcomes
- phase ii
- double blind
- locally advanced
- cerebrospinal fluid
- brain injury
- papillary thyroid
- subarachnoid hemorrhage
- platelet rich plasma
- replacement therapy
- allogeneic hematopoietic stem cell transplantation
- cerebral ischemia
- chronic lymphocytic leukemia