Good morning, myeloma world.

It's Monday, and the weekend definitely is over. The vigorous activity in our email inbox is making that eminently clear. But, with the week still so young, there isn't much new myeloma research for us to review with you. In fact, we have just two new studies that we'd like to discuss today.

Both studies are by European researchers who have compiled and analyzed retrospective data on some important topics.

One study out of Portugal looks at the use of Revlimid (lenalidomide) to treat multiple myeloma patients who have severe kidney impairment.

A second study is by researchers in England. They look at how effective Velcade (bortezomib) is when it is used in patients who have been previously treated with the drug.

We also have some feedback we'd like to share with you from myeloma specialist Dr. Philip McCarthy. It concerns two studies we recently covered about the use of allogeneic stem cell transplantation in multiple myeloma patients.

Finally, we would be remiss if we didn't mention that the U.S. Food and Drug Administration today approved Venclexta (venetoclax, ABT-199, GDC-0199) as a new treatment for chronic lymphocytic leukemia (CLL) (FDA press release; and additional FDA information).

Although Venclexta's approval is for CLL, we mention the FDA decision because Venclexta also has been investigated as a potential multiple myeloma therapy. See, for example, this poster from last year's American Society of Clinical Oncology (ASCO) meeting, and abstracts #3038 and #4219 from last year's American Society of Hematology (ASH) meeting.

The Use Of Revlimid In Patients With Severe Kidney Impairment

Background

About a fifth of multiple myeloma patients have kidney damage when they are diagnosed. Much of the time, the kidney damage is a result of the patient's multiple myeloma. The disease can cause very high levels of protein and calcium in the blood, which can damage kidneys.

It is therefore important that treatments used with myeloma patients be safe for their kidneys. It also is important to understand how kidney damage affects the amount of a drug in a patient's blood, because kidneys often play a key role in how the body removes (excretes) drugs from the blood, organs, and tissue.

The International Myeloma Working Group (IMWG) recently issued recommendations for the diagnosis and management of multiple myeloma patients with kidney impairment (abstract).

The New Study

The Portuguese study we mentioned earlier is a multi-center retrospective analysis. It examines outcomes for 23 patients with relapsed/refractory multiple myeloma and severe kidney impairment (creatinine clearance less than 30 mL/min). The 23 patients were treated with Revlimid and dexamethasone (abstract).

Almost two thirds of the patients were on dialysis when they started their Revlimid-dexamethasone treatment. The patients had a median of 2 prior lines of therapy, were a median of 62 years of age when diagnosed, and a median of 68 years of age when they started Revlimid-dexamethasone treatment.

Median follow-up of the patients from the start of treatment with Revlimid and dexamethasone was 52 months. The overall response rate to treatment was 56 percent, which, according to the researchers, is in line with previously published data.

The median duration of therapy was 14 months. Median event-free survival was 20.5 months and median overall survival 42.6 months.

Nine percent of patients experienced improvement in their renal function, but no patients who started treatment on dialysis became dialysis independent.

The main side effects were related to blood cell counts, but the authors felt the treatment was “well tolerated.”

Overall, the authors feel that Revlimid and dexamethasone, when used in patients such as those discussed in their study, can generate “significant response outcomes” and an overall survival benefit, “with manageable toxicities.”

Retreatment With Velcade

The second study we will look at today is a short report by a team of physicians based at University College in London, England.

The London researchers examine treatment outcomes for 23 patients who, at their first relapse, were given a Velcade-based regimen as treatment. This meant, however, that all patients were being retreated with Velcade, because they also had received a Velcade-based treatment as initial therapy after diagnosis.

(And, yes, we noticed that this study – like the one we discussed previously – also involves 23 patients. Weird.)

So, what were the outcomes of retreatment with Velcade?

A bit more than three quarters of the 23 patients were treated with a Velcade-based three-drug regimen at relapse. This was about the same proportion of patients who received a "triplet" as part of their initial treatment after diagnosis. Patients had to achieve at least a partial response to their initial therapy, by the way, to be part of this retreatment study.

Almost 90 percent of the patients (87 percent) had at least a partial response to Velcade retreatment at first relapse. Median time to progression after the start of retreatment was 14.4 months, compared to 18.9 months between the start of first treatment and initial relapse.

More patients experienced peripheral neuropathy during retreatment than during initial treatment (61 percent versus 48 percent).

“This single centre study in real life patients,” the authors conclude, “demonstrates that [Velcade] combinations used at first line and sequentially at first relapse represent a valid treatment strategy for selected patients.”

We should mention before moving on that, in the United States, Velcade is officially approved to be used to retreat myeloma patients who have been previously treated with the drug (related press release).

Dr. Philip McCarthy On Two Recent Allogeneic Stem Cell Transplantation Studies

Regular Myeloma Morning readers will recall that we recently reported on two different studies related to allogeneic (donor) stem cell transplantation in multiple myeloma patients. One study was a report by Dutch researchers on long-term allogeneic transplant outcomes (Myeloma Morning – April 1, 2016). The other was by researchers in Wisconsin reporting on the impact of high-risk status and minimal residual disease status on transplant outcomes (Myeloma Morning – April 6, 2016).

Although we covered the two studies in different editions of Myeloma Morning, they were published at about the same time. When they were published, we asked myeloma specialist Dr. Philip McCarthy for his thoughts about them. Here is what he told us:

“There are certain patients that seem to benefit long term from allogeneic transplantation, but we do not have a good idea exactly who they are. We know that those who are in remission do better than those with refractory disease. Both studies confirm this. So, it becomes all the more important to determine which patients should get an allogeneic transplant and who benefits the most. The BMT CTN [Blood and Marrow Transplant Clinical Trials Network ] is examining the role of allogeneic transplantation in high-risk multiple myeloma patients with a randomization to placebo or ixazomib (Ninlaro) after transplant. This will be an important study for determining if ixazomib maintenance after allogeneic transplant will improve long-term outcome.

“So, we know that high risk disease as determined by molecular gene expression profiling or staging using, for example, the revised ISS score will identify very high risk patients who could be considered for early allogeneic transplantation. What we need to know is who will have long-term disease control, and possibly cure, via allogeneic transplantation. The majority of transplant-eligible patients still are best treated with standard induction therapy followed by autologous transplantation and maintenance.”

Dr. McCarthy is the director of the Blood and Marrow Transplant Center at Roswell Park Cancer Institute in Buffalo, New York. He also was the lead investigator in the Phase 3 “CALGB 100104” clinical trial that investigated Revlimid maintenance therapy after autologous stem cell transplantation.

New Myeloma-Related Research Articles

1. João, C. et al., “Lenalidomide is effective and safe for the treatment of patients with relapsed multiple myeloma and very severe renal impairment” in the Annals of Hematology, April 11, 2016 (abstract)
2. Reyal, Y. et al., “Real world experience of bortezomib re-treatment for patients with multiple myeloma at first relapse” in the British Journal of Haematology, April 8, 2016 (full text)