January 9, 2017 | by Abe Rosenberg
Lowell Winer remembers the moment when he realized he was cured.
“I was ecstatic,” he said. “I'd worked so hard for this, and here it was.”
Diagnosed with Hodgkin lymphoma at age 35, the former digital media specialist from Venice, California, believed he was young and strong enough to be among the lucky 50 percent who beat the disease with conventional treatment. He was wrong.
Over the next four years, Winer endured several cycles of chemotherapy and two autologous transplants, none of which worked for very long. In the meantime, he suffered all the physical and emotional side effects of treatment, from nausea and hair loss to vanishing stamina. And then he got the bad news.
“All the repeated failures had felt like a medicine ball to the gut,” he recalled. “But after the transplants failed, I was told I had maybe two years left to live.”
Everything changed when Winer joined a phase 2 clinical trial examining the effectiveness of brentuximab vedotin (BV) after a failed transplant. The BV worked immediately, achieving a complete remission which, year after year, proved to be durable beyond anyone's expectations.
“Frankly, we were surprised,” said Robert Chen, M.D., assistant professor with City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation, who led the trial. “Nobody thought patients could actually be cured this way. We assumed we'd eventually have to resort to a donor transplant, a much riskier procedure. It's wonderful to be able to offer patients a better choice.”
Brentuximab vedotin is a relatively new and very different kind of cancer treatment. It is a targeted therapy that seeks out cancer cells and destroys them without harming healthy cells or triggering the physically challenging side effects of conventional chemotherapy.
What makes BV so different is its construction. It is an antibody-drug conjugate, or ADC, a powerful chemo drug bonded to an antibody that recognizes a protein called CD30 that's often present in Hodgkin lymphoma cells. In the bloodstream, this ADC ignores normal cells, but attaches itself to the CD30 protein. Once there, the chemo drug separates from the antibody, enters the cancer cell and obliterates it.
While BV has been around since 2011 and subjected to dozens of clinical trials, this phase II study was the first time the drug was tested in patients after a failed transplant. The results, published in mid-2016, were nothing less than stunning.
A total of 102 patients with the CD30 protein received BV in the trial. Thirty-four achieved complete remission, while 13 of those 34 have remained disease-free for more than five years and may be considered cured. While some of those patients also received further chemo or a donor transplant, for nine patients the news is truly remarkable:
“It is critical to note that nine of the complete-response patients have been in remission for over five years after receiving only brentuximab vedotin,” said Chen. “The fact that these patients are doing so well, even five years out, provides a new perspective for prognosis.”
It's rare to hear conservative, cautious researchers talking about a cure. And yet, the long-term results for BV have so excited this community, it's tempting to ask the obvious question: Are we approaching the day when targeted therapy will eliminate the need for standard chemo and transplants?
“It's way too early for that,” cautioned Chen.
But it's not too early to accelerate research into other uses for BV.
One upcoming trial will test BV in combination with ibrutinib (a drug commonly used to treat some forms of leukemia) in patients with relapsed/refractory Hodgkin lymphoma. Another trial will target patients who've shown resistance to BV, which often happens (a pumping mechanism in the cancer cells expels the anti-cancer drug). These patients will receive an MDR-1 inhibitor designed to stop that pumping mechanism.
All this new research will add to the formidable body of knowledge surrounding BV, the first truly new Hodgkin lymphoma treatment in decades. Researchers have already determined that BV works as an effective consolidation therapy immediately after a transplant, working to kill remaining cancer cells and minimize the risk of a relapse. BV is also being studied as a frontline treatment, replacing one of the four highly toxic ABVD chemotherapy drugs typically given to Hodgkin lymphoma patients as a first line of attack.
“This is a very exciting time to be in the treatment of Hodgkin lymphoma," Chen said, adding that future research will investigate ADCs as a possible treatment for other lymphomas, as well as leukemia and multiple myeloma.
Winer shares that excitement. After years of living in what he calls “survival mode,” he's gradually been able to reprogram his thinking and start planning his future.
“It took some time, because the whole process was pretty sobering,” he said. “Remember, many of the patients in that trial didn't make it, and I could have been one of them. Instead, I'm getting physically stronger every year, and mentally I've finally landed in a fantastic place.”
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