The May issue of AJHO highlights how progress in one type of malignancy can inform another. This is especially important in rarer cancers, so called “orphan diseases,” where the body of literature and number of patients available for trials are quite low and limits the generation of definitive recommendations and the development of new drugs. The update on acute lymphocytic leukemia (ALL) by Drs Short and Jabbour highlights the developments and current base of evidence with newer therapies, in particular, the importance of targeting CD20 with rituximab. Further emphasis on the importance of this target comes from the development and approval of other anti-CD20 antibodies. This was initially witnessed by the sweeping change in the management of B-cell malignancies, starting with B-cell lymphomas, extending to chronic and acute B-cell leukemias. More recently, as described by Dr Gertz in an accompanying review on Waldenström macroglobulinemia (WM), rituximab is now being used as a part of combination therapy effectively for this disease, long marked by its inexorable progression and refractoriness to therapy. Other examples of drugs imported for use in WM from other B-cell-derived malignancies include bendamustine, approved for CLL and relapsed lymphoma, the Bruton tyrosine kinase inhibitor ibrutinib for mantle cell lymphoma and CLL, as well as bortezomib and lenalidomide approved for multiple myeloma. In fact, the approval of ibrutinib for WM would not have been possible without the information from other diseases, as the basis for its accelerated approval for WM was a phase II trial with only 63 patients. Ibrutinib is the only FDA approved drug specifically for WM (even though as pointed out in the WM review, many other standards exist), so it is likely that additional drug approvals for this disease will emanate from other cancers of similar lineage.
This brings us back to the review of new active drugs for ALL—other CD20 antibodies such as ofatumumab, the anti-CD19 bispecific T-cell engager blinatumomab, and the anti-CD22 antibody-drug conjugate inotuzumab ozogamicin. All these antigens are also expressed on WM. This along with drugs tested successfully for more common B-cell malignancies may hold promise for WM and also be relevant across a spectrum of these related diseases. Hopefully, these examples will be repeated for other orphan cancers—this will require the continuation of robust drug development in general with cross-communication across expertise in other cancers, dedication to continued innovation with smaller and smarter trials for rarer malignancies and special pathways through the FDA.
Debu Tripathy, MD