Continuing coverage from ASCO 2015. A SERMO Oncologist provides brief commentary on several excellent education session talks today on hematologic malignancies in older adults.
Acute Lymphoblastic Leukemia (ALL) in Older Patients–David Marks. ALL in older patients has 15-20% long term survival, with no major improvements recently. Bad cytogenetics, more Ph-positivitgy, and more primary refractory dz account for this. TP53 (p53) mutation is frequently associated with early relapse. Poor vincristine tolerance, more problems with steroids, and polypharmacy also contribute. The elderly have a 4X higher induction mortality. Marks reviewed the UK ALL 60+ trial results, with 19/23 CRs, but 11 therapy stoppages and 13 deaths. His suggestions for comorbid patients are to decrease steroid doses, attenuate daunorubicin, give G-CSF support, and consider ritux if CD20+. Also, be cautious with azoles. Geriatric assessments are coming to this field. In the UK ALL 14 study, RIC allografts have promising 70% OS at 16 months.
My take: this is a very challenging disease, and it is always hard to balance treatment aggressiveness with tolerability, especially for geriatric patients.
CAR T cell therapy for Acute Lymphoblastic Leukemia (ALL)–Michael Sadelain. Dr. Sadelain reviewed the MOA and design of chimeric antigen receptor (CAR) T cells. CARs are chimeras of CD28, CD3, and TCR components, and their DNA is added to that of the patient’s own T cells, allowing the T cells to attack particular antigens (in the case of ALL, it’s CD19). T cells are collected by apheresis, activated, transduced with retroviral vectors, and are ready after 10 days. Then they are infused or frozen. The regimen requires 3 g/m2 cytoxan conditioning. CR rates are high (70-90%) but toxicity can be high, too (cytokine release syndrome).
My take: probably too rough for the elderly, but this will be a key treatment in the future for getting refractory-disease patients to transplant.
There was a session on treatment of hematologic malignancies in older adults. Joachim Deeg, Paul Hamlin, and Maxwell Krem were the speakers, covering Myelodysplastic Syndrome (MDS), Diffuse Large B-Cell Lymphoma (DLBCL), and indolent NHL (Non-Hodgkin’s Lymphoma), respectively. Common themes were that aging is bad, in terms of problematic comorbidities, adverse effects, and bad outcomes. Age impacts survival even when stratifying by risk scores. Comprehensive geriatric assessments may be better than performance status for predicting bad outcomes. There are also some regimens for DLBCL that may be substitutes for RCHOP if anthracycline must be avoided (R-GCVP, R-miniCEOP). In iNHL, ibrutinib and idelalisib are promising. This is a rapidly evolving and potentially confusing treatment landscape. You can still aim for cures, but you must weigh patient-specific factors carefully!
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