Immunotherapies. Thus far most oncologists would classify them as an oh so promising bust. They work in the lab. They should work in human patients. Should have, would have, could have. But finally, after decades of trying, researchers are starting to figure things out–and the results are impressive!
I want to share excerpts from an article, ASCO: Immune Therapy Wins Praise, by Charles Bankhead, Staff Writer for MedPage Today. Normally I would post this on my more general HelpWithCancer.org site, because it doesn’t address myeloma directly. But I wanted you to get a feeling for how progress using immunotherapy is gaining steam in oncology; myeloma immunotherapy research simply hasn’t caught-up:
CHICAGO — A fifth of heavily pretreated patients with advanced cancers responded to a monoclonal antibody that blocks a tumor’s ability to hide from the immune system, a preliminary clinical study showed.
Overall, 21% of patients had objective responses to MPDL3280A, which targets the tumor protein PD-L1. An analysis limited to patients who had PD-L1-positive tumors showed that more than a third responded to the monoclonal antibody.
About 90% of responding patients continued to respond during follow-up for as long as 15 months, reported Roy S. Herbst, MD, of Yale University.
OK. Impressive but not a bombshell. But check-out the unusually broad range of cancers that MPDL3280A (They have got to come-up with a better name!) has helped:
Herbst reported findings for 171 patients, 140 of whom could be evaluated for response. The study population included patients with lung cancer, kidney cancer, melanoma, colon cancer, stomach cancer, and head and neck cancer, and the patients had received a median of three prior therapies.
Patients received the monoclonal antibody intravenously every 3 weeks and continued until disease progression or development of unacceptable toxicity. Response was assessed every 6 weeks for 6 months and then every 12 weeks…
Overall, 29 of 140 (21%) patients had objective responses, including 13 of 36 (36%) patients whose tumors tested positive for PD-L1. Responses were observed across the spectrum of tumor types represented in the trial.
Treating solid tumors tends to be exceedingly difficult, especially after they have metastasized. This is truly impressive stuff!
And how about this? The article goes on to discuss an exciting new way of treating skin cancer:
Another immunotherapeutic strategy led to objective responses in 40% of patients with previously treated stage III and IV (metastatic) melanoma. The treatment regimen consisted of ipilimumab (Yervoy), an approved treatment for melanoma, and the investigational agent nivolumab. Studies involving preclinical models suggested the combination has more activity than either agent alone, said Jedd D. Wolchok, MD, of Memorial Sloan-Kettering Cancer Center in New York City…
Overall, 40% of patients in the concurrent group had objective responses, including tumor reductions of 80% or more in 16 (31%) patients. Complete responses occurred in 17% of patients. The most active regimen consisted of ipilimumab at the approved dose of 3 mg/kg and nivolumab 1 mg/kg, which led to objective responses in nine of 17 patients (53%), including 80% or greater reduction in tumor size in seven (41%) patients.
The inclusion of patients with slow responses and stable disease increased the clinical benefit rate to 65%.
WOW! Metastasized melanoma is stubborn stuff! And note these great results are a result of combining drugs, something myeloma researchers have been capitalizing on for years.
But I’ve saved the best for last:
A first-in-class small molecule inhibitor led to rapid, major lymph node responses in about two-thirds of patients with heavily pretreated chronic lymphocytic leukemia (CLL). The patients received idelalisib (formerly GS1101), a specific inhibitor of PI3K-delta, which is the predominate isoform in an aberrantly hyperactivated signaling pathway that drives CLL.
The phase I study involved patients with relapsed/refractory CLL, which has few treatment options, said Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute in Boston. The 54 patients in the trial had received a median of five prior regimens, and 70% were refractory to their most recent regimen.
Overall, 50 of 54 patients had some degree of tumor regression, and most had at least 50% shrinkage, qualifying as objective responses.
“Idelalisib rapidly induced deep and durable lymph node responses in the vast majority of patients,” said Brown. “The nodal responses appeared to be independent of the very high-risk mutations, deletion 17p or TP53.”
As a myeloma patient, I’m jealous! Why can’t myeloma researchers match results like this?
Maybe they can! Elotuzumab was our first, best hope. While it does show some measurable benefit when combined with Revlimid, it was a flop by itself.
Fast forward to a newer anti-myeloma immunotherapy drug, daratumumab. In an early, single agent study (no dex or assist from another novel therapy) daratumumab produced results similar to the first example I shared above. You know, the one that’s yet unnamed with the long research designation, MPDL3280A. If you recall, it produced results in 21% of heavily pretreated patients with solid tumors.
Well, according to results posted in abstract 8512 at ASCO, 8 out of 32 patients responded to daratumumab. I’m not good at math, but my trusty calculator tells me that’s a 25% response rate.
This bodes well for the possibilities of combining daratumumab with one or more additional therapies to gain a synergistic affect; like adding dexamethasone to Revlimid and/or Velcade. Or, for that matter, I wonder if adding dex to daratumumab might help, too?
With the help of supercomputers and collaborative work from researcher’s worldwide (the daratumumab study involves patients from four or five different countries), I’m confident that scientists might finally make meaningful progress on the immunotherapy front.
Results revealed at last year’s ASCO hinted at a number of immunotherapy breakthroughs. This year’s early data suggests progress is real and speeding-up exponentially.
Great news, don’t you think?
Feel good and keep smiling! Pat