Here’s how readers responded to a You Make the Call question about treatment options for a transplant-ineligible patient with Philadelphia chromosome-positive (Ph+) acute lymphocytic leukemia (ALL).
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I would suggest continuing “POMP”-style maintenance chemotherapy with prednisolone, vincristine, 6-mercaptopurine (and rituximab if CD20 positive, as was suggested in the clinical information). The patient should also receive intrathecal chemotherapy.
In addition to this, the patient should continue on a TKI with monthly quantitative polymerase chain reaction testing. If the BCR-ABL transcripts remain at a low level and continue to decline, dasatinib could continue, but we would have a very low threshold for switching to ponatinib. With the BCR-ABL transcripts at a very low level, commencing at just 15 mg per day and continuing would be reasonable (rather than the 45 mg daily dose), given the high incidence of thrombosis and noting this patient’s comorbidities.
Also, it may be worthwhile to highlight the high risk of morbidity and mortality with initial hyper-CVAD–type therapy. The Germans have presented on this and recommend starting at lower dose chemotherapy with a TKI, which has been found to provide better short-term results with the same long-term disease control.
Julian Cooney, FRACP, FRCPA, MBBS
I would recommend checking a BCR-ABL mutational analysis to guide a change in the TKI. If no mutations are detected, I would switch to ponatinib 30 mg daily (a dose associated with less toxicity).
Reshma Ramlal, MD
I would recommend treatment with blinatumomab and a TKI.
Sabine Gerull, MD
Based on the results of the GIMEMA study by Robin Foà, et al., a combination of blinatumomab and a TKI would be a less toxic option. Testing of the primary Ph+ ALL clone towards different TKIs or defining the point mutation might support a change to another TKI.
Revisiting the bone marrow sample at diagnosis, including cell sorting to identify an underlying CML, would support an allogeneic hematopoietic cell transplantation. However, the patient’s condition doesn’t allow this.
I would not start with CAR T-cell therapy in this case because of the complete remission. That might be an option at relapse.
Friso Calkoen, MD
I would consider two options. The first is ponatinib plus dexamethasone, given the higher potency of ponatinib. This extrapolates from the CALGB 10701 study of TKI plus dexamethasone, which might have similar response rates compared to cytotoxic chemotherapy. While on ponatinib, I would give antiplatelet therapy to prevent thrombosis. The second option is blinatumomab, which has a U.S. Food and Drug Administration approval for measurable residual disease positivity in this setting.
Shyam A. Patel, MD, PhD