Andrew D. Zelenetz, MD, PhD, on Treating the Elderly Lymphoma Patient With Elevated Bilirubin

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Andrew D. Zelenetz, MD, PhD

While the older patient with large cell lymphoma and elevated bilirubin may have a somewhat worse prognosis that some, he still has the potential for a curative outcome.

—Andrew D. Zelenetz, MD, PhD

At the 19th Annual Conference of the National Comprehensive Cancer Network (NCCN), lymphoma expert and NCCN Panel Chair on Lymphoma, Andrew D. Zelenetz, MD, PhD, fielded questions from oncologists. The ASCO Post was there to capture his recommendations for a common clinical scenario—treating the elderly patient with elevated bilirubin. Dr. Zelenetz is Vice Chair of the Department of Medicine and former Chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, New York.

Clinical Scenario

The patient is an 80-year-old who presented with monoclonal gammopathy. At 3 months’ follow-up, he had weight loss and jaundice, with splenic and liver lesions, a bilirubin of 10 mg/dL and climbing, and an ejection fraction of 40%. The biopsy revealed large cell lymphoma that was CD20-positive. How would you treat this patient?

“For the older patient with elevated bilirubin, you have a few good options, some of them rather surprising,” Dr. Zelenetz said.

The obvious option, “which is easy,” he added, is to give rituximab [Rituxan] (375 mg/m2), high-dose prednisone (100 mg), and cyclophosphamide (1.0–1.2 g/m2). “Don’t worry that this dose of cyclophosphamide is too high; you are not giving an anthracycline. The goal for this cycle is not to provide definitive therapy but to get adequate cytoreduction to reduce the bilirubin and permit definitive treatment,” he explained.

Once the bilirubin has dropped (it need not completely normalize), a reasonable chemotherapy option in a patient with suitable cardiac function is R-mini-CHOP [prednisone at 40 mg/m2 on days 1–5, rituximab at 375 mg/m2 on day 1, doxorubicin at 25 mg/m2 on day 1, cyclophosphamide at 400 mg/m2 on day 1, vincristine at 1 mg/m2 on day 1]. “R-mini-CHOP has been used in patients with ejection fractions as low as 45% and the results are remarkably good, so this is a reasonable option for older patients,” he maintained.

Less Conventional Options

A new and “surprising” option is to substitute gemcitabine for the anthracycline in R-CHOP, according to Dr. Zelenetz. This involves gemcitabine at 750 mg/m2 for the first cycle, increasing to 875 mg/m2, then to 1,000 mg/m2 by the third cycle if tolerated, for six cycles; all cycles are supported by growth factors. The results in terms of progression-free and overall survival are similar to those seen with R-mini-CHOP, and, importantly, outcomes are not diminished in patients with low ejection fractions, making this a good choice for elderly patients, he indicated.

The third approach is rather unconventional, Dr. Zelenetz acknowledged. The patient is treated from day 1 with dose-adjusted EPOCH-R (etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab). “Because of the dosing of the drugs by continuous infusion over 96 hours, you can give full doses and you never get to a very high Cmax. The ejection fraction is maintained so you don’t get cardiac toxicity, and you do not have issues with drug clearance,” he pointed out.

“We give dose-adjusted EPOCH-R from the get-go, with doses based on nadir counts. You can use either pegfilgrastim [Neulasta] or filgrastim [Neupogen]; they are associated with the same rate of dose adjustments,” he said.

“The other regimen that is remarkably good in older patients—even patients over the age of 90—is rituximab/gemcitabine/oxaliplatin (R-GemOx),” he continued. R-GemOx (rituximab at 375 mg/m2 on day 1, gemcitabine at 1,000 mg/m2 on day 2, oxaliplatin at 100 mg/m2 on day 2) is very well tolerated in older patients, which Dr. Zelenetz acknowledged is somewhat unexpected.

“I was nervous the first time I gave this to a patient, but he flew through it without a problem, and since then I have treated a series of older patients with this regimen. In fact, R-GemOx has become my go-to treatment for relapsed or refractory disease in the older patient who is not a transplant candidate,” he said.

R-GemOx is now included in the NCCN Guidelines, he added, and there are no problems with reimbursement now that oxaliplatin is available generically. Dr. Zelenetz said he gives this regimen to any patient who is not a transplant candidate, “which at Memorial is a patient age 70 or older, but we have given this to patients in their 90s,” he added.

Not Recommended

One regimen that is being used by some clinicians but is not recommended by Dr. Zelenetz is bendamustine (Treanda)/rituximab. “According to market research, this regimen began to be commonly used in older patients with large cell lymphoma in the relapsed/refractory setting, in the absence of published data. But now there have been two studies in de novo large cell lymphoma, and while the overall response rates are pretty good, the response duration is miserably short,” he said.

“While the older patient with large cell lymphoma and elevated bilirubin may have a somewhat worse prognosis that some, he still has the potential for a curative outcome,” he emphasized. “I would not recommend bendamustine/rituximab. I would use one of the three curative regimens I described.” ■

Disclosure: Dr. Zelenetz has received research support from Genentech/Roche, Gilead, Janssen/Pharmacyclics, and Bristol-Myers Squibb, is a consultant for Genentech/Roche, Gilead, Sanofi-Aventis, Hospira, and Dr. Reddy Laboratories, and is on the scientific advisory board for Lymphoma Research Foundation and Cancer Genetics Institute.