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May 16, 2014

A Fresh Approach to Bone Marrow Transplant in Older Patients

Myeloconditioning offers a new alternative to age 55+ patients with blood cancers.

A Fresh Approach to Bone Marrow Transplant in Older Patients

Bone marrow transplant is the only potentially curative treatment option for older AML patients, but patients over the age of 55 are frequently ineligible for conventional care. [vetpathologist – Shutterstock]

  • Bone marrow transplants are currently a $1.3 billion market,1 representing the fastest-growing hospital procedure in the United States. They are the only potential cure for many blood cancers such as acute myeloid leukemia (AML) in older patients. The procedure is technically called hematopoietic stem cell transplantation (HSCT) and can be either a bone marrow transplant (BMT) or transplant of blood stem cells isolated from peripheral blood (PBSCT). In either case, it involves transplanting cells capable of restoring normal bone marrow function into a patient.

    An increasing number of HSCT patients are over the age of 55, but many in this group who need the procedure are ruled ineligible. This is due to the fact that the high-dose chemotherapy that traditionally precedes HSCT—which is standard therapy for younger patients—is often deemed too harsh even for healthy looking older people. Indeed, in certain indications, less than 10 percent of those age 55+ survive more than a year after conventional HSCT. The best results in terms of leukemia-free survival have essentially benefited younger patients. In older patients, HSCT often results in unacceptable transplantation-related mortality due in part to the toxicity of the regimens used in conditioning prior to transplant.

    Since more than two thirds of AML patients are over the age of 55,2 new tactics are clearly needed. For example, what if sufficient killing power can be delivered almost exclusively to cancer cells, bone marrow, and other organs where these cells reside while avoiding the damage caused to the rest of the body by high-dose chemotherapy?  This promising approach, known as “radioimmunotherapy,” is now being pursued by various medical researchers.

  • A Promising Alternative

    Radioimmunotherapy is one of several investigational approaches that are being explored for patients who are considered unfit for intensive chemotherapy. Various clinical studies have indicated that precisely targeted radioimmunotherapy could result in longer survival and a reduction of the risks associated with traditional therapy.

    Reduced-intensity myeloconditioning regimens with radioimmunotherapy can be safely administered even in patients who would not be candidates for conventional HSCT. To see why use of targeted therapies represents a promising approach, they can be compared to cytotoxic chemotherapy, which remains a mainstay of cancer treatment even though its use is limited by its substantial killing of normal cells in addition to cancerous ones. Over the last 15 years targeted therapies underwent vast expansion and their biggest segment is represented by mAbs. Several mAbs for treating different cancers have been approved by the FDA and have been very commercially successful. According to The New York Times, Herceptin, a breast cancer mAb, was the bestselling drug used only for cancer in 2012 when it recorded approximately $6.3 billion in sales and Avastin, approved in 2004 and indicated in a number of cancers, also recorded approximately $6.3 billion in sales during that same year.

    However, despite their commercial success, mAbs have limited potency, as evidenced by the fact that out of hundreds of antibodies under development, relatively few have been approved by the FDA for sale in the United States. Even though they are excellent at targeting cancer cells, mAbs often lack sufficient killing power to eradicate these cells completely. The relatively new approach to treating cancer is to combine the precision of targeting molecules with the proven killing power of radiation or cytotoxic chemotherapy by attaching powerful killing agents—referred to as “payload”—to precise molecular carriers, mostly mAbs. Three key categories of payloads are alpha-emitting radioisotopes, beta-emitting radioisotopes and cytotoxic chemotherapeutics.

    With any cancer treatment, success is usually increased when treatment initiates soon after diagnosis. This is especially true in refractory and relapsed leukemia patients whose projected survival is only a few months if they don’t undergo a bone marrow transplant. Waiting for half that time to transplant them can have a serious impact. Treatment with radioimmunotherapy reduced-intensity conditioning has been shown to prepare a patient for bone marrow transplant in only 10 days, compared to approximately six weeks required with traditional care—a potentially vital difference in the face of a fast-evolving cancer.

    The significance of this approach comes into focus in light of the fact that the only potentially curative treatment option for older AML patients is bone marrow transplant, but the majority of patients over age 55 are ineligible for conventional care due to health reasons and/or severity of their disease. It seems plausible that radioimmunotherapy compounds offer a new alternative to patients who ran out of them. Almost all patients are eligible, and preliminary studies indicate their survival rates are significantly higher than in those patients treated with currently used modalities. 

    Although the value of radioimmunotherapy in blood cancers is still being studied, several teams have already treated a number of patients in clinical trials including, specifically, relapsed and refractory leukemia patients over age 50. Further, this therapy has been also applied in younger patients and in both younger and older patients in first complete remission. There has so far been no randomized study addressing the question of the comparison of reduced-intensity radioimmunotherapy with traditional treatment, although some are being planned. However, analyses have shown that reduced-intensity radioimmunotherapy in patients with AML older than 50 is feasible and is associated with less transplant toxicity.

  • Beyond Bone Marrow

    The promise of radioimmunotherapy goes far beyond bone marrow transplants. A technology co-developed with Memorial Sloan Kettering Cancer Center relies on the power of alpha emitters, a special class of radioisotopes, to kill hidden cancer cells with doses of radiation so low that they are undetectable in the body. In many cancers, a small group of cells remains secluded and out of reach of current therapies, and that’s why some cancers return after being put into remission.

    If radioimmunotherapy compounds continue to perform well in clinical trials, it could result in a new paradigm of treatment for older patients seeking BMTs, offering a fresh and potentially effective treatment for a patient population sorely in need of new options. The next few years might bring hope of a cure to older patients who currently have little to no options.

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