He recommended consideration of comorbidities and use of a comprehensive geriatric assessment when contemplating care options for this age group. “We want to make sure that the therapy used matches the patient before us,” he added, pointing to an algorithm that is helpful in this setting (Blood. 2013;122:1366-75).
“Where it’s possible, I would encourage the use of clinical trials, particularly geared to the older age population. And that said, in the older, fitter patient with a good initial response to therapy, do not discount the appropriateness of allogeneic stem cell transplant,” Dr. Alvarnas advised.
At the same time, hematologists should have a frank discussion with these older patients about the goals of care and advanced directives, and should involve supportive care early.
“NCCN has an absolutely beautiful document on the care of older oncology patients as well as a beautiful set of guidelines regarding supportive care,” he added. “Please look at those. I think are an invaluable resource.”
Immunotherapy shows promise in the salvage setting
“At the time of salvage, immunotherapy-based approaches are very powerful, so don’t overtreat the patient with modalities that aren’t going to work,” Dr. Alvarnas recommended.
“Immunotherapeutic approaches are going to play an increasingly important role in patients with ALL, and we see these novel therapeutics completely upending what we knew about this disease even a year or two ago,” he said. A variety of monoclonal antibodies against CD20, CD19, CD22, and CD52 have shown promise when tested in various patient populations (Blood. 2015;125:4010-6).
This concept has been taken a step further with blinatumomab (Blincyto), an antibody having two antigen recognition sites that brings CD19-positive tumor cells in contact with T lymphocytes. It is the first such agent to be approved by the FDA for an ALL indication (currently for refractory or relapsed Ph-negative B-cell ALL). “It has nonoverlapping activity with cytotoxic chemotherapy, which makes it an ideal agent,” Dr. Alvarnas noted.
The main risk with blinatumomab is a cytokine release syndrome, which is most common in patients with a high disease burden and requires drug discontinuation and treatment with high-dose dexamethasone. Neurotoxicity is also noteworthy as it can be fatal.
Responses to blinatumomab tend to be dramatic and deep, but brief, according to Dr. Alvarnas. “Even though it’s profoundly powerful, it’s not a curative agent. It really provides a bridge towards cure, with that cure coming through the use of allogeneic stem cell transplant,” he elaborated. “So if someone relapses and you begin blinatumomab, get them referred very quickly to a transplant center.”
Another promising immunotherapy is inotuzumab ozagamicin, an antibody-drug conjugate that targets CD22-expressing cells. It has been associated with a complete response rate of 19%, although veno-occlusive toxicity has been problematic (Cancer. 2013;119:2728-36). “This agent has not yet received FDA approval, but it’s one that we are awaiting expectantly,” he said.
Finally, phase 1 trials from various academic centers have shown that chimeric antigen receptor (CAR) T-cell therapy achieves complete response rates of 67%-90% in patients with high-risk refractory disease, according to Dr. Alvarnas, who disclosed that he had no relevant financial relationships.
“This has lead to culmination in phase 2 trials, and I really do see this as an important component in the management of patients with relapsed and refractory ALL,” he concluded. “It’s not something that is available at every center. Right now it’s restricted largely to academic centers capable of producing these therapeutics in their own GLP [Good Laboratory Practice] facility.”