ASCO 2013 And Multiple Myeloma: What Were The Highlights?
This year’s meeting of the American Society of Clinical Oncology (ASCO) was held May 31 through June 4 in Chicago.
During the meeting, The Beacon published daily updates that provided overviews of the important multiple myeloma findings presented during the meeting.
Now that the meeting has concluded, the focus shifts to the bigger picture: What were the key findings of the meeting? Were there results with immediate implications for the treatment of multiple myeloma? Did the research at the meeting represent a major step forward for myeloma patients, or was it more incremental in nature?
To address these questions, the Beacon Staff conducted its own in-depth review of the meeting’s research, and it also consulted with a number of myeloma specialists.
In particular, The Beacon received feedback about the meeting from myeloma specialists Dr. Amrita Krishnan from City of Hope, Dr. Shaji Kumar from the Mayo Clinic, Dr. Paul Richardson from the Dana-Farber Cancer Institute, Dr. Frits van Rhee from the Myeloma Institute for Research and Therapy, and Dr. Ravi Vij from Washington University School of Medicine.
The Bottom Line: Incremental Steps In The Right Direction, But Nothing Game Changing
Overall, there was some good news for myeloma patients and caregivers that came out of this year’s ASCO meeting.
But as is typically the case, there was not as much research presented at ASCO as there was at the past American Society of Hematology (ASH) meeting, and none of the ASCO research can be considered earth-shattering.
Nonetheless, there were some highlights to the ASCO meeting.
There was encouraging research on the potential myeloma treatment quisinostat, which has not received much attention in the past, and which works differently than existing myeloma therapies such as Revlimid (lenalidomide) and Velcade (bortezomib).
There also were updates about potential treatments that have been discussed at previous meetings, and which continue to show promise. Treatments in this category include daratumumab, elotuzumab, and ixazomib (MLN9708).
In addition, there continued to be good news about Kyprolis (carfilzomib) and Pomalyst (pomalidomide), which were recently approved as new myeloma therapies by the U.S. Food and Drug Administration (FDA). In particular, the results of one of the Pomalyst studies will likely lead to approval of the drug in Europe.
These developments mean that the list of treatment options available to myeloma patients and specialists can be expected to grow in the coming years. More treatment options, in turn, are likely to result in further improvements in the survival of myeloma patients. And that is definitely good news.
Yet, from the perspective of a myeloma patient, it seems difficult to argue that the results presented at the ASCO meeting rise to a level beyond “good.”
As promising as the many new myeloma treatments are, there was no convincing evidence that any of them will be real game changers.
Dr. Vij seemed to agree when he said “There was nothing very path-breaking on myeloma at ASCO.”
Furthermore, most of the new treatments presented at ASCO are a number of years away from being readily available to most myeloma patients. Elotuzumab is likely to be the first of these drugs to be approved for myeloma, and its approval is not expected until later next year, at the earliest.
In addition, a number of key controversies related to the treatment of multiple myeloma still remain unanswered: How many treatments and which treatments should be used for newly diagnosed patients? Should all transplant-eligible patients undergo stem cell transplantation at some point during the course of their disease, and if so, what is the optimal timing of transplantation? Is maintenance therapy beneficial, and if so, how long should it be administered?
The myeloma specialists The Beacon consulted identified a few studies that attempted to shed some light on these questions. One study, for example, compared stem cell transplantation with novel agent therapy and also investigated the benefits of maintenance therapy. Another study evaluated a new technique for detecting minimal residual disease, which could help physicians determine which patients should receive further treatment. Neither of these studies, though, settled any of the key controversies.
New Agents Being Tested For Myeloma
Highlights from the ASCO meeting certainly included research results for a number of new myeloma therapies.
Results presented at the meeting ranged from promising initial clinical trial results for one new drug, quisinostat, to updated results from early-stage clinical trials for a couple of drugs, to updated results from a late-stage clinical trial for elotuzumab.
Although clinical trial results were presented at ASCO for a number of new treatments being investigated for myeloma, quisinostat was the only one that made its first appearance at ASCO (poster [PDF] courtesy of Dr. Xavier Leleu).
Referring to a study about quisinostat and another study of the related drug panobinostat, Dr. van Rhee said, “The histone deacetylase inhibitors panobinostat and quisinostat when combined with Velcade and dexamethasone [Decadron] were reported to induce responses in relapsed and refractory, including Velcade-refractory, myeloma patients.”
Although the rest of the new myeloma treatments in this article are ones that have been discussed at several previous medical meetings, the updated results presented at this year’s ASCO meeting demonstrate that these drugs continue to show promise as myeloma treatments.
Among the new drugs the myeloma specialists mentioned as particularly promising, an antibody known as daratumumab was the only one mentioned by almost all of the myeloma specialists The Beacon consulted about the ASCO meeting (presentation [pdf] courtesy of Dr. Lokhorst).
Dr. van Rhee explained that although daratumumab is earlier in development than elotuzumab, “Daratumumab is of interest since it exhibited single-agent activity in relapsed and refractory patients during a dose-escalation study and induced partial responses.”
“Daratumumab's data continues to look exciting regarding response rates,” said Dr. Vij.
Dr. Kumar also stated that it is “very interesting data, and daratumumab clearly appears to be a promising drug.” He pointed out, however, that “concerns remain about infusion reactions and isolating the effect of the antibody from the steroids” which patients also have received during treatment with daratumumab.
Elotuzumab in combination with Revlimid and low-dose dexamethasone continued to demonstrate high response rates and favorable progression-free survival in relapsed and refractory patients (poster [PDF] courtesy of Dr. Sagar Lonial).
“Elotuzumab showed good activity in the relapsed / refractory setting in combination with dexamethasone and Revlimid,” said Dr. van Rhee. “Phase 3 studies are presently recruiting,” he added.
Dr. Vij indicated that the results of this Phase 3 study could be practice changing.
“In a Phase 1 study, the oral proteasome inhibitor ixazomib was well tolerated and showed activity in a heavily pre-treated patient population without causing severe neuropathy,” explained Dr. van Rhee. Neuropathy is nerve damage that can cause pain, tingling, and numbness in the hands and feet.
“Weekly ixazomib data shows the drug has single-agent activity in relapsed and refractory disease,” said Dr. Vij. He, as well, noted that the drug has low rates of peripheral neuropathy.
Dr. Kumar also remarked that ixazomib has “promising single-agent activity, and neurotoxicity appears limited.” He pointed out, though, that the data “needs validation from larger patient groups treated for longer periods.”
Pomalyst And Kyprolis
A number of studies involving Pomalyst (pomalidomide) and Kyprolis (carfilzomib) were discussed at this year’s ASCO meeting. The FDA approved both of these drugs within the last year for the treatment of relapsed and refractory myeloma.
The latest data on these two drugs continue to support their effectiveness. One study, however, indicates Kyprolis should be used with caution in patients with existing serious heart disease.
“Several studies [presented at ASCO] support the notion that the recently approved drugs Pomalyst and Kyprolis are contributions to the armamentarium for relapsed / refractory myeloma including patients with moderate [kidney] impairment and adverse cytogenetics [chromosomal abnormalities],” said Dr. van Rhee.
The efficacy and safety of Pomalyst plus low-dose dexamethasone were discussed during a number of ASCO presentations. The combination therapy was compared to treatment with high-dose dexamethasone alone, and it also was evaluated in specific subsets of relapsed and refractory myeloma patients such as older patients, those with kidney impairment, and those with chromosomal abnormalities.
“A randomized Phase 3 study showed improved overall survival for patients treated with Pomalyst and low-dose dexamethasone who had failed both Revlimid and Velcade,” said Dr. van Rhee. The improved survival was in comparison to treatment with high-dose dexamethasone alone (presentation [pdf] courtesy of Dr. Katja Weisel).
These results are good news for European myeloma patients. Dr. Vij stated that these results “will lead to approval of the drug [Pomalyst] in Europe.”
Dr. Krishnan also cited the importance of a Phase 1 study that indicates Pomalyst plus Velcade and low-dose dexamethasone is effective for relapsed and refractory myeloma patients (poster [PDF] courtesy of Dr. Paul Richardson).
Dr. van Rhee said, “Kyprolis continues to show promising results both in newly diagnosed patients and in the relapsed / refractory setting, including patients who failed Revlimid or Velcade.”
The only specific Kyprolis study that any of the myeloma experts mentioned, though, is a retrospective analysis that showed nearly a fifth of heavily pretreated myeloma patients who received treatment with Kyprolis experienced heart-related complications. Most of these patients had preexisting risk factors for heart-related complications. The researchers therefore suggest using Kyprolis with caution in patients with a history of serious cardiac disease (poster [pdf] courtesy of Dr. Saad Usmani).
“As we are using the drug in more patients and earlier in the disease course, this information is important in patient selection for the drug as well as in monitoring for side effects,” said Dr. Krishnan.
Stem Cell Transplantation And Maintenance Therapy
Another study was mentioned by almost all of the myeloma specialists The Beacon consulted about the ASCO meeting. It is one that evaluated the importance of stem cell transplantation as well as maintenance therapy (presentation [pdf] courtesy of Dr. Palumbo).
All patients in the study received initial therapy with four cycles of Revlimid and dexamethasone. After that, half the patients were randomly selected to receive consolidation therapy with melphalan (Alkeran), prednisone, and Revlimid (MPR), while the other half received consolidation with high-dose melphalan followed by an autologous (own) stem cell transplant.
After their consolidation therapies, the patients were once again randomized to receive either no maintenance therapy or maintenance therapy with Revlimid.
Dr. Vij summarized the results by saying, “Transplantation is superior to MPR according to progression-free survival, and maintenance therapy is superior in terms of both progression-free survival and overall survival.” He pointed out, however, that the design of the study makes interpretation of the maintenance data difficult.
Dr. Kumar agreed that the study “highlights the value of transplantation as a consolidation [therapy].” He did not feel, however, that six cycles of MPR therapy was really sufficient therapy, going so far as to say that the the patients who received that therapy, combined with no maintenance therapy, received "very inadequate therapy."
He therefore cautions that no conclusions should be drawn from the study except that “transplantation is still an effective consolidation, and short duration of Revlimid-dexamethasone therapy plus MPR is not to be used.”
Minimal Residual Disease
Almost all of the myeloma specialists also highlighted a study reporting on the use of a new method, known as deep sequencing, to detect minimal residual disease (MRD) in myeloma patients (abstract). The technique may be able to detect more cases of residual myeloma than the most common current method of determining MRD status, multiparameter flow cytometry.
Similar to previous studies, the results of the deep-sequencing study show that patients with no residual disease after treatment have better overall survival than those who still have residual disease.
Dr. Krishnan said that the results are “very interesting in further proof of principle that therapy to get to an MRD-negative state may be our new goal. Though, it still begs the question how best to achieve that result, e.g., induction plus transplantation and consolidation, multidrug induction alone, etc.”
Dr. van Rhee added that “Prospective studies will have to address the question whether MRD can be used both to guide the type of therapy administered and the duration of treatment.”
Although the deep-sequencing study was broadly seen by the myeloma specialists The Beacon surveyed as one of the highlights of the ASCO meeting, not all of them feel deep sequencing is a significant improvement.
Dr. Kumar described deep sequencing as “promising technology,” but pointed out that it is still limited by the need for baseline samples. Dr. Vij went a step further, saying that he did not feel the deep-sequencing study demonstrated that the new technology is superior to multiparameter flow cytometry.
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All of The Beacon’s coverage related to the ASCO 2013 meeting can be found here.
Note: Electronic copies of conference presentations and posters made available to the Beacon's readers are for personal use only. Further transmission or publication of the files is not permitted, although hyperlinks to the files are permitted with attribution to the author and to The Beacon (for example, "courtesy of Dr. Jane Doe and The Myeloma Beacon.")
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- ASCO 2013 Multiple Myeloma Update – Day Four: Oral Presentations
- Multiple Myeloma And The ASH 2012 Meeting: Taking Stock And Tagging The Highlights
- ASCO 2013 Multiple Myeloma Update – Day Three: Poster Presentations