How would you treat an adult patient with T-cell lymphoblastic lymphoma with FGFR1 rearrangement and co-exisiting myeloproliferative neoplasm?

This is a rare condition only recently recognized as its own diagnostic entity by the WHO as part of a larger family of disorders referred to not-concisely as "myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2" (Arber et al., PMID 31659364). I think these disorders are akin to CML in that they are likely stem-cell disorders driven primarily by an oncogenic gene rearrangement/fusion that can transform into acute leukemia of either myeloid or lymphoid lineage. Why there seems to be a tendency for these disorders to evolve into T lymphoblastic lymphoma/leukemia is beyond my understanding.

Before speaking about treatment, it should be emphasized that no treatment to my knowledge is specifically approved for these rare disorders. Thus, one can only discuss off-label prescribing of medications for which relatively little data exist to support their use.

While little is known about their optimal treatment, experts seem to agree that including a targeted agent that can block signaling of the affected oncogene (again, similar to blast phase of CML) seems prudent (Reiter and Gotlib; PMID 28028030). Those with FGFR1 fusions have historically been harder to target. ABL kinase inhibitors, including ponatinib, have limited activity when used as single agents, though cases exist where ponatinib was combined with hyperCVAD with some success (Khodadoust et al., PMID 26055304). There is an ongoing single-arm study of the FGFR inhibitor pemigatinib in this disease, preliminary results from which have shown some signs of efficacy [FIGHT-203; Verstovsek, et al. Blood 2018;132 (Supplement 1):690]. While pemigatinib is now FDA-approved for the treatment of biliary-tract cancer and thus potentially available, eligible patients should be encouraged to participate in this trial if available.

Given the historically poor prognosis with standard therapies, fit patients who are interested in pursuing curative-intent therapy should be considered for referral for allogeneic transplantation (Strati et al., PMID 29119847). 

In summary, I would treat a patient with newly-diagnosed T lymphoblastic lymphoma/leukemia and an FGFR1 fusion with hyperCVAD + ponatinib and recommend allogeneic HCT if remission is achieved. I would consider pemigatinib for relapsed/refractory disease, ideally in the context of a prospective trial.