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.