What happens to intolerant, relapsed or refractory chronic myeloid leukemia patients without access to clinical trials?

Abstract

Objective To assess clinical outcomes of intolerant, relapsed or refractory patients who could not be treated with new tyrosine kinase inhibitors or experimental therapies. Methods A retrospective cohort of 90 chronic myeloid leukemia patients in all phases of the disease treated with imatinib mesylate as their first TKI therapy, and with dasatinib or nilotinib as the next line of therapy. We evaluated clinical outcomes of these patients, with special focus on the group that needed more than two therapy lines. Results Thirty-nine percent of patients were refractory or intolerant to imatinib. An 8-year overall survival rate of the patients who went through three or more lines of treatment was significantly lower, compared to those who were able to maintain imatinib as their first-line therapy (83% and 22%, respectively p < 0.01). Decreased overall survival was associated with advanced-phase disease ( p < 0.01), failure to achieve major molecular response in first-line treatment ( p < 0.01) and interruption of first-line treatment due to any reason ( p = 0.023). Failure in achieving complete cytogenetic response and major molecular response and treatment interruption were associated with the progression to the third-line treatment. Conclusion The critical outcome observed in relapsed, intolerant or refractory chronic phase CML patients reflects the unmet need for this group of patients without an alternative therapy, such as new drugs or experimental therapies in clinical trials. Broader access to newer treatment possibilities is a crucial asset to improve survival among CML patients, especially those refractory or intolerant to first-line therapies.

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL

“…For patients with CML-CP who are intolerant of or resistant to ≥2 prior TKIs, therapeutic options become limited due to newly emerging mutations, existing comorbidities, or toxicities associated with previous treatments [1,4,5]. With each subsequent line of TKI treatment, failure rates increase, including the risk of progressing to advanced phases of the disease [6][7][8][9][10][11]. Patients who require treatment with multiple TKIs may experience severe and/or irreversible adverse events (AEs) due to off-target effects and lack of specificity of ATP-competitive TKIs [1,12].…”

Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results

“…As patients without satisfactory treatment outcomes advance through successive lines of TKIs, treatment failure rates increase, survival rates decrease [13,15,16], and many do not achieve optimal responses [1,2,10,[17][18][19][20][21][22][23][24]. New treatment options with improved antileukemic activity and long-term tolerability are needed for patients with resistance or intolerance to multiple TKIs.…”

Long-term outcomes of third-line therapy with tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: A real-life experience

“…The significance of the depth of cytogenetic response before third-line therapy was also assessed in the study of Bosi et al. ( 22 ), where among the 13 patients who failed to respond to first- and second-line therapy, six with cytogenetic response before third-line therapy achieved a deeper cytogenetic response and higher overall survival on third-line TKI therapy.…”