ASH 2013 Multiple Myeloma Update - Day Three: Afternoon Oral Sessions

Monday was the third day of this year’s meeting of the American Society of Hematology (ASH). The day was filled with oral presentation sessions from early in the morning until into the evening.
In the afternoon and early evening, there were six oral presentation sessions devoted solely to multiple myeloma and a number of other myeloma-related presentations scattered about the afternoon. The topics of these presentations ranged from the biology of myeloma to treatment options for newly diagnosed, relapsed and refractory, and older patients.
This ASH update highlights most of the oral presentations from Monday afternoon and evening that discussed treatment options for myeloma patients.
Treatment Options For Newly Diagnosed Multiple Myeloma
Ixazomib Plus Revlimid And Dexamethasone
Dr. Paul Richardson from the Dana-Farber Cancer Institute presented results from a Phase 1/2 study of ixazomib (MLN9708) in combination with Revlimid (lenalidomide) and dexamethasone (Decadron) in newly diagnosed myeloma patients (abstract, slide deck [PDF]).
Among the 56 patients treated with the Phase 2 dosing, 95 percent responded, with 21 percent achieving a stringent complete response, 5 percent a complete response, 11 percent a near complete response, 38 percent a very good partial response, and 20 percent a partial response.
The median duration of response was 14 months.
Although the overall response rate in this trial was quite high, some may nonetheless be disappointed with the results.
The share of patients in the trial who achieved a very good partial response or better, 75 percent, is lower than what has been seen in trials testing Kyprolis (carfilzomib), Revlimid, and dexamethasone in newly diagnosed patients, where 81 percent to 88 percent of the patients have had at least a very good partial response (see a description of one of the studies below in this article as well as related Beacon news about the other study and article in Blood).
Additionally, the rate of peripheral neuropathy (pain, tingling, or loss of sensation in the extremities) for the ixazomib, Revlimid, and dexamethasone regimen (53 percent of patients) was not as low as was observed with the Kyprolis-based regimen (23 percent).
Kyprolis-Revlimid-Dexamethasone Plus Revlimid Maintenance
Dr. Neha Korde from the National Cancer Institute and the National Institutes of Health presented updated results from a Phase 2 trial of Kyprolis, Revlimid, and dexamethasone followed by Revlimid maintenance therapy for newly diagnosed myeloma patients (abstract).
Among the 43 patients included in the study, 98 percent responded, with 51 percent achieving a stringent or complete response, 16 percent a near complete response, 21 percent a very good partial response, and 9 percent a partial response.
Among all the patients who reached at least a near complete response, 100 percent of those tested were negative for minimal residual disease.
The one-year progression-free survival rate was 97 percent.
Dr. Korde also reported that the regimen was an effective and tolerable regimen for older patients.
Revlimid-Cyclophosphamide-Dexamethasone For Newly Diagnosed Myeloma Patients
Dr. Charlotte Pawlyn from the Institute of Cancer Research in London presented results from a study comparing Revlimid-cyclophosphamide (Cytoxan)-dexamethasone (RCD) and thalidomide (Thalomid)-cyclophosphamide-dexamethasone (TCD) as induction therapy for newly diagnosed multiple myeloma patients (abstract).
As part of the study, 1,507 younger, healthier patients were given an intensive RCD or TCD regimen, and 1,162 older, frailer patients were given a non-intensive RCD or TCD regimen. Younger, healthier patients then underwent stem cell transplantation.
Dr. Pawlyn reported results for patients treated with RCD.
Overall, 84 percent of the patients responded to intensive RCD therapy and 73 percent responded to non-intensive RCD therapy. The depth of responses, however, was lower than what is seen in studies where Revlimid is combined with proteasome inhibitors such as Velcade and Kyprolis and dexamethasone. In the current study, the share of patients achieving a very good partial response or better was 61 percent for the intensive RCD therapy and 53 percent for the non-intensive RCD regimen.
Nevertheless, the study investigators conclude that these early results suggest that Revlimid-cyclophosphamide-dexamethasone may be an effective and safe frontline treatment for newly diagnosed multiple myeloma patients of all ages.
Treatment Options For Older, Newly Diagnosed Multiple Myeloma
Kyprolis-Cyclophosphamide-Dexamethasone
Dr. Sara Bringhen from the University of Torino in Italy reported results from a Phase 2 study evaluating Kyprolis, cyclophosphamide, and dexamethasone as initial therapy for older, newly diagnosed multiple myeloma patients (abstract). After initial therapy, patients received further Kyprolis maintenance therapy.
The overall response rate was 96 percent, with 64 percent reaching at least a complete or near complete response, 12 percent a very good partial response, and 20 percent a partial response.
The two-year progression-free survival rate was 76 percent, and the overall survival rate was 87 percent.
According to Dr. Bringhen, Kyprolis-cyclophosphamide-dexamethasone therapy compares very favorably to other treatment options for older patients, both in terms of efficacy and safety.
Revlimid-Dexamethasone Versus Revlimid-Melphalan-Prednisone Or Revlimid-Cyclophosphamide-Prednisone
Dr. Antonio Palumbo from the University of Torino presented results from a study comparing the efficacy of Revlimid-dexamethasone (Rd) versus Revlimid-melphalan-prednisone (MPR) or Revlimid-cyclophosphamide-prednisone (CPR) in older, newly diagnosed multiple myeloma patients (abstract).
Overall response rates for the three regimens were similar (72 percent to 74 percent). Responses appeared to be somewhat deeper for MPR and Rd than for CPR.
There was a trend toward better median progression-free survival for MPR (27 months) compared to CPR (24 months) and Rd (22 months) and a trend toward better two-year overall survival for CPR (84 percent) compared to MPR (81 percent) and Rd (80 percent).
Side effects were significantly less common with CPR and Rd.
Therefore, Dr. Palumbo and his colleagues recommend CPR for fit patients, Rd for unfit patients, and low-doses of Rd for frail patients.
Reduced-Dose Velcade-Based Therapies
Dr. Stefania Oliva from the University of Torino reported results from a Phase 2 study assessing the efficacy and safety of three reduced-dose Velcade-based treatments in older patients with newly diagnosed multiple myeloma (abstract).
Patients received reduced-dose treatment with Velcade plus prednisone (VP), Velcade plus cyclophosphamide and prednisone (VCP), or Velcade plus melphalan and prednisone (VMP).
The overall response rates were 67 percent for those who received VP, 67 percent for VCP, and 80 percent for VMP. Patients treated with VMP also achieved deeper responses.
The median progression-free and overall survival times were similar for the three treatment groups; however, the rate of discontinuation due to side effects was higher for patients treated with VMP compared to those treated with VP and VCP.
Scoring System For Older Multiple Myeloma Patients
Dr. Antonio Palumbo also spoke about a new scoring system that can be used to predict survival and the risk of severe side effects in older newly diagnosed multiple myeloma patients (abstract).
Overall, 869 older myeloma patients who had been enrolled in three prospective clinical trials testing Revlimid-, Velcade-, and Kyprolis-based initial therapies were included in the retrospective analysis. The median age was 74 years.
Researchers used information including age, co-existing diseases, and cognitive and physical conditions to identify three categories of patients: fit, unfit, and frail.
The researchers found that outcomes after treatment were consistently worse among unfit and frail older patients compared to fit older patients. The higher mortality rates in unfit and frail patients seem to be due, to an important degree, to the greater risk of severe side effects among such patients.
The researchers therefore believe physicians should use an assessment such as the one they have developed to determine the general health of older newly diagnosed myeloma patients, and then tailor treatment based on the assessment. Older frail patients, for example, should probably be given two-drug regimens rather than more intensive three-drug regimens.
Treatment Options For Relapsed And Refractory Myeloma
Kyprolis-Pomalyst-Dexamethasone
Dr. Jatin Shah from MD Anderson Cancer Center in Houston presented updated findings from a Phase 2 trial investigating Kyprolis-Pomalyst (pomalidomide, Imnovid)-dexamethasone treatment for relapsed and refractory myeloma (abstract, slide deck [PDF]).
Among the 67 heavily pretreated patients included in the study, 70 percent responded, with 27 percent achieving a very good partial response and 43 percent a partial response.
The median progression-free survival was 9.7 months, and the median overall survival was not yet reached at 18 months.
Dr. Shah reported that treatment outcomes for study participants with high-risk chromosomal abnormalities were at least as good as those seen in patients without such abnormalities.
Pomalyst Plus Low-Dose Dexamethasone Versus High-Dose Dexamethasone Alone
Dr. Jesús San Miguel from the University Hospital in Salamanca, Spain, reported results from the Phase 3 study comparing Pomalyst plus low-dose dexamethasone to high-dose dexamethasone alone for heavily pretreated multiple myeloma (abstract). This is the study that led to the approval of pomalidomide, marketed under the brand name Imnovid, in Europe.
The overall response rate was significantly higher for patients receiving Pomalyst plus low-dose dexamethasone (32 percent) compared to patients receiving high-dose dexamethasone (11 percent).
Dr. San Miguel reported that progression-free and overall survival were significantly better for Pomalyst plus low-dose dexamethasone.
The median progression-free survival was 4.0 months for Pomalyst plus low-dose dexamethasone and 1.9 months for high-dose dexamethasone; the median overall survival was 13.1 months for the Pomalyst-based regimen and 8.1 months for high-dose dexamethasone.
Pomalyst Plus Dexamethasone In High-Risk Myeloma Patients
Dr. Xavier Leleu from the Hopital Claude Huriez in Lille, France, reported results from a multicenter Phase 2 trial evaluating the efficacy and safety of Pomalyst plus dexamethasone in relapsed and refractory multiple myeloma patients with the chromosomal abnormalities del(17p) and/or t(4;14) (abstract).
Prior studies have shown that this combination regimen has a response rate of 30 percent to 40 percent and extends time to progression in relapsed and refractory myeloma patients. However, patients in those studies with del(17p) and/or t(4;14) chromosomal abnormalities demonstrated much shorter median times to progression.
The current study included 50 relapsed and refractory multiple myeloma patients who had del(17p) and/or t(4;14).
The overall response rate was 22 percent; 32 percent for patients with del(17p) and 16 percent for patients with t(4;14). The median time-to-progression was 2.9 months: 7.3 months for del(17p) and 2.8 months for t(4;14). The median overall survival was 12 months: 12 months for del(17p) and 9.2 months for t(4;14).
These findings, along with those from Dr. Shah's study described above in this article as well as another ASH presentation that will be discussed in a Beacon article tomorrow, indicate that Pomalyst is more effective for myeloma patients with the del(17p) chromosomal abnormality than was previously realized.
Indatuximab Ravtansine Plus Revlimid And Dexamethasone
Dr. Kevin Kelly from the University of Texas Health Science Center in San Antonio presented results from a Phase 1/2a study of indatuximab ravtansine (BT062) in combination with Revlimid and dexamethasone in relapsed and refractory myeloma patients (abstract)
Among the 15 patients currently evaluable for response, the overall response rate was 73 percent, with 13 percent achieving a complete response, 27 percent a very good partial response, and 33 percent a partial response. The remaining 22 percent achieved stable disease. The overall response rate was similar among patients who were refractory to previous Revlimid-dexamethasone therapy.
Ricolinostat Plus Velcade
Dr. Noopur Raje from Massachusetts General Hospital presented results from a Phase 1b trial of ricolinostat (ACY-1215) plus Velcade and dexamethasone for relapsed and refractory myeloma (abstract, slide deck [PDF]).
The study included 20 very heavily pretreated myeloma patients. Overall, 25 percent responded to therapy, with 10 percent achieving a very good partial response and 15 percent a partial response. Among the patients who were resistant to previous Velcade therapy, 10 percent responded to the ricolinostat combination therapy.
Long-Term Survivors Of Multiple Myeloma
Dr. Ronald Go from the Mayo Clinic presented results from a retrospective study describing clinical characteristics of long-term survivors of multiple myeloma (abstract). In this study, long-term survivors were defined as those who survived 10 or more years after their diagnosis.
A total of 27,982 multiple myeloma patients diagnosed between 1998 and 2000 were identified in the National Cancer Data Base. Of these patients, 8 percent were long-term survivors. Compared to patients who did not survive at least 10 years past their diagnosis, long-term survivors had a significantly higher proportion of patients younger at diagnosis, with high educational level, initial treatment at an academic center, and an autologous stem cell transplant as part of initial therapy. When interpreting the result in regard to transplantation, however, it should be noted that novel anti-myeloma agents such as Velcade and Revlimid were not available when the long-term survivors in this study received initial therapy.
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More myeloma presentations from Day 3 and Day 4 of the ASH 2013 meeting also will be summarized in a final ASH daily update to be published at The Beacon tomorrow. Additional coverage of key research results from the meeting will continue in individual, topic-specific news articles. For a list of all myeloma-related ASH abstracts, a schedule of the myeloma-related ASH sessions, and all Beacon articles related to this year’s ASH meeting, see The Beacon’s ASH 2013 Myeloma Gateway.
Related Articles:
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Adding Clarithromycin To Velcade-Based Myeloma Treatment Regimen Fails To Increase Efficacy While Markedly Increasing Side Effects
- Importance Of Factors Affecting Multiple Myeloma Survival Changes With Patient Age