https://orcid.org/0000-0001-7391-7168
In this issue of Blood Global Hematology, Pagnano et al1 describe the results from a limited number of patients treated with asciminib for advanced chronic myeloid leukemia (CML). Asciminib has been shown to be a highly effective and safe medication for CML in various stages of therapy.2 The results from good centers are not unexpectedly different from those elsewhere or from studies with similar patients. However, do we have all the information we need to come to a conclusion? What needs to be looked at carefully is the nature of the response.
The findings in this group of patients were not unexpected. Intolerant patients responded better to all drugs than resistant patients did. Patients with T315I mutations did poorly, with only 1 of 7 achieving major molecular remission (MMR). With the exception of 1 patient who had an allograft, blast crisis was not controlled well and death occurred. Only a third of the patients achieved MMR or better. Toxicity was good given that they were a heavily treated cohort of patients.
Asciminib was supplied on a compassionate basis. According to colleagues in Brazil, patients with CML for the most part, with the exception of those with good private care, have issues obtaining consistent supplies of quality medications. Were the patients in this study adequately treated before becoming resistant as a result? Most patients were still in the chronic phase when asciminib was started, but the molecular response at baseline for them was not given, just that they were in hematological remission. All those achieving MMR or better were in chronic phase at the time of starting asciminib. Did they improve their molecular response? If not, did they, in fact, really improve with asciminib?
As a segue, let us conduct a reality check on CML care in Brazil and probably the entire resource limited world. Why use these drugs if molecular response is not improved notably when there are greater overall demands? The goals of CML therapy can be simplified when we look at newly diagnosed patients. First, it is survival, then treatment-free remission (TFR) if possible, and then dealing with therapy related complications in the long term. The first goal has an easy answer. If patients are compliant, then the survival of newly diagnosed patients with CML is nearly that of age-matched controls.3 As reviewed recently in the American Society of Hematology Education 2025 session, survival has not improved beyond that.4 In fact, even the depth of response beyond 1% international standard does not seem to improve survival, and thus, is pushing for deeper response needed? However, identifying a drug for initial therapy and monitoring patients remain as issues.
Second, TFR is only a reality for individuals achieving the appropriate deep molecular responses early and for patients such as those in this study, but for advanced therapy, this is currently not an option.
The third goal is the long-term safety of therapy. In the short term at least, asciminib appears to be a highly safe medication, but it is extremely early to comment on any long-term issues.
Do not misunderstand me. Asciminib is an excellent medication, with good efficacy and at least at this point in time and as this real-world study shows, good tolerance. When used appropriately, it is the drug of choice. Parachuting it into situations where more resource-friendly options are available is questionable. Its use in CML beyond first line is appropriate and cost effective. There are other medications that have also fit these efficacy and safety criteria with longer follow-up that are also options.5-7
In most of the world where resources are stretched, cost is an issue regardless of the method of reimbursement. Thanks to the good graces of pharmaceutical companies, worldwide, many patients have access to some CML drugs and monitoring through compassionate programs. However, they are obviously a minority of all the patients who could be eligible. At the recent CML Horizons Conference 2025 in Bucharest, a meeting of patients with CML and CML advocates, I listened to the issues faced by patients around the world (eg, reliable and stable access to quality drugs, access to monitoring, dealing with side effects, and distance to physicians). Many patients, and I am sure this is underestimated, cannot even obtain any drug. Universal access to therapy and monitoring is where we should be concentrating our efforts and resources. There are important initiatives to address this issue, but I fear that efforts will hit only the tip of the iceberg. Yes, we do need better drugs for those truly eligible, but we do need the availability of any drugs for those who are needy, and this is a much greater need overall and where resources should be directed.
In the meantime, while we are trying to solve the world’s resource imbalances, studies such as this reported here need to be conducted to make physicians comfortable with the use of new drugs as they wishfully will become available to all.
Conflict-of-interest disclosure: J.H.L. is or has been a consultant to and received research funding from Novartis, Bristol Myers Squibb, Takeda, and Pfizer.
