Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p deletion

Abstract

Although uncommon in treatment-naive patients with chronic lymphocytic leukemia, deletion 17p is a high-risk disease characteristic. We analyzed and reported outcomes for 63 patients with deletion 17p chronic lymphocytic leukemia who received first-line therapy at our institution; at time of first treatment, 81% had unmutated immunoglobulin heavy chain variable gene and 58% had complex karyotype. Forty-nine patients (76%) received first-line fludarabine, cyclophosphamide, rituximab-based therapy, 6 (11%) received rituximab-based and 8 (13%) received lenalidomide-based treatment. Overall, the complete plus nodular partial remission rate was 33%; on multivariable model, higher complete plus nodular partial remission rate was observed in patients with less than 50% cells positive for deletion 17p, and a higher probability of achieving at least a partial remission was observed with fludarabine, cyclophosphamide, rituximab-based treatment. After a median follow up of 33 months (range 1-89 months), the estimated median progression-free survival was 14 months (95% confidence interval 10-18) and estimated median overall survival was 63 months (95% confidence interval 43-83). In multivariable analysis, factors independently associated with longer progression-free survival were response to treatment and absence of complex karyotype. Achievement of complete plus nodular partial remission rate and mutated immunoglobulin heavy chain variable gene were independently associated with longer overall survival in multivariable model. Complex karyotype was associated with increased risk for Richter's transformation. New first-line strategies and agents must aim at both improving response and maintaining remission in patients with deletion 17p, particularly in the presence of complex karyotype.

Role of allogeneic transplantation in patients with chronic lymphocytic leukemia in the era of novel therapies: a review

“…This therapy is thus of marginal benefit in patients with 17p deletion. At MD Anderson, a study done combining FCR with granulocyte macrophage colony-stimulating factor showed that the ORR was 100% with a significant reduction in infectious complications [Strati et al 2014]. Reduced doses of FCR, such as FCR-lite, are also available which are well tolerated in the older population [Foon et al 2009].…”

Diagnosis and classification of hematologic malignancies on the basis of genetics

“…65 Patients with 17p deletions or TP53 mutations have the worst prognosis and poor survival when treated with standard therapy; however, the novel Bruton tyrosine kinase (BTK) inhibitor ibrutinib has improved outcomes in this particular group of patients. 66,67 In addition to cytogenetic alterations, discrimination of CLL patients on the degree of mutation of the immunoglobulin heavy-chain variable-region (IGHV) gene also has prognostic and therapeutic importance. A mutated IGHV in CLL has long been associated with favorable outcome and was recently shown to be a key predictor of long-term remissions with chemoimmunotherapy.…”

Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study

“…Ibrutinib was administered orally at a dose of 420 mg once daily and continued until disease progression or unacceptable toxicity. Ofatumumab was administered intravenously per prescribing information (300 mg for dose 1/2000 mg for doses [2][3][4][5][6][7][8][9][10][11][12]. Patients could then continue daily ibrutinib in extension study PCYC-1103-CA until progression or intolerability.…”

“…Moreover, the presence of highrisk features such as unmutated immunoglobulin heavy chain variable region (IGHV), del(17)(p13.1), or transformation to high-grade lymphoma is associated with poor outcomes. [4][5][6][7][8][9][10] Thus, new and effective regimens are needed for patients with pretreated CLL.…”