This year’s meeting of the American Society of Hematology (ASH) began yesterday morning in New Orleans.

Myeloma-related presentations were made during several sessions yesterday.

Two sessions were designed to better educate physicians about multiple myeloma and how to treat the disease.

The key myeloma-related research presented yesterday was made public during a poster session in the evening about the biology of myeloma as well as pre­clin­i­cal and clin­i­cal studies testing new and existing treat­ments for myeloma.

During the session, research results were made avail­able for review by meeting attendees in the form of posters, each of which summarized the results of a single study. As is typically the case during such sessions, each poster was about two feet high by three or four feet in length. All the posters — of which there were literally hundreds — were displayed in an exhibit hall covering an area larger than a football field.

Education Sessions

Three presentations were given by myeloma experts during the morning’s Education Session.

The first talk was given by Dr. Ola Landgren from the National Cancer Institute and National Institutes of Health.  Dr. Landgren spoke about biological insights into the myeloma precursor diseases mono­clonal gam­mop­athy of undetermined sig­nif­i­cance (MGUS) and smol­der­ing multiple myeloma.  He also discussed treat­ment strategies for high-risk smol­der­ing myeloma, also more recently being called early myeloma.

Dr. Maria-Victoria Mateos from the University Hospital of Salamanca in Spain gave the second presentation.  Dr. Mateos discussed how to treat newly diag­nosed myeloma patients, particularly those who are in­eli­gible for stem cell trans­plan­ta­tion.

The final talk of the session was given by Dr. Philip McCarthy from Roswell Park Cancer Institute.  Dr. McCarthy con­tinued Dr. Mateos’ discussion of how to treat myeloma patients, focusing on treat­ment options for trans­plant-eligible myeloma patients.

In a separate session later in the morning, Dr. Andrzej Jakubowiak from the University of Chicago Medical Center further con­tinued the discussion of how to treat multiple myeloma patients.

Posters About Combinations Of Approved Therapies

A number of posters presented results from clin­i­cal studies testing com­bi­na­tions of already approved anti-myeloma drugs.

In particular, there were several studies of Kyprolis (car­filz­o­mib)-based com­bi­na­tions as well as several studies of Pomalyst (poma­lido­mide, Imnovid)-based com­bi­na­tions.

One poster summarized results from a Phase 1 study of once-weekly (rather than twice-weekly) Kyprolis plus dexamethasone (Decadron) for re­lapsed or refractory myeloma (abstract).  The results show that two-thirds of the patients responded to weekly Kyprolis and dexa­meth­a­sone ther­apy, which compares favorably to the 55 per­cent to 60 per­cent response rate seen with twice-weekly Kyprolis. The median time to response was one month, which the investigators described as rapid.

Results were also presented from a Phase 1/2 study of Kyprolis in com­bi­na­tion with mel­phalan and pred­ni­sone for older newly diag­nosed myeloma patients (abstract).  Overall, 91 per­cent of patients responded, with 55 per­cent achieving at least a very good partial response.  The median event-free survival was 22 months, and the two-year over­all survival was 84 per­cent.  In addi­tion, only 6 per­cent of the study par­tic­i­pants devel­oped mod­er­ate or severe periph­eral neu­rop­athy (pain, tingling, or loss of sensation in the extremities), making it a safe and effective option for older patients.

Another poster summarized results from a pilot study of Kyprolis in com­bi­na­tion with Revlimid (lena­lido­mide) and dexa­meth­a­sone followed by extended Revlimid dosing for high-risk smol­der­ing myeloma (abstract).  Among the 12 patients eval­u­ated for response, all achieved at least a near com­plete response.  In addi­tion, 92 per­cent had no minimal residual disease detected.

Two studies of Pomalyst in com­bi­na­tion with Velcade (bor­tez­o­mib) and dexa­meth­a­sone for re­lapsed or refractory myeloma were presented during tonight’s poster session (abstract and abstract).  In the two studies, 71 per­cent to 94 per­cent of patients, in­clud­ing those resistant to pre­vi­ous Revlimid ther­apy, responded to the Pomalyst-based com­bi­na­tion.

Another poster summarized results from a Phase 2 study of Pomalyst in com­bi­na­tion with clarithromycin (Biaxin) and dexa­meth­a­sone for re­lapsed or refractory myeloma (abstract).  Overall, 61 per­cent of study par­tic­i­pants responded, and 56 per­cent of patients pre­vi­ously resistant to both Revlimid and Velcade ther­apy responded.  The median pro­gres­sion-free survival was 9 months, more than double the pro­gres­sion-free survival of Pomalyst plus dexa­meth­a­sone alone, and the median over­all survival was 19 months.

Another study presented at tonight’s poster presentation session looked at how prior Revlimid or thalidomide (Thalomid) ther­apy affected response to Pomalyst (abstract).  The results show that patients whose last line of ther­apy con­tained Revlimid or thalido­mide are less likely to respond to Pomalyst (29 per­cent response rate com­pared to 44 per­cent for those who did not receive either of these drugs in their last line of ther­apy) and their median duration of treat­ment was also shorter (5.7 months versus 7.3 months).  Among those pre­vi­ously treated with Revlimid or thalido­mide at any point, those who had a shorter duration of Revlimid or thalido­mide treat­ment and those who had more time be­tween Revlimid/thalidomide treat­ment and start of Pomalyst treat­ment were more likely to respond to Pomalyst.

Another study that looked at sequencing of Pomalyst and Kyprolis (abstract) suggests that heavily pre­treated patients achieve deeper responses if treated first with Kyprolis and then with Pomalyst; how­ever, the researchers state that longer follow-up is needed to assess duration of response before any conclusions can be drawn.

In addi­tion, several posters were presented this evening that reported on Velcade and Revlimid studies.

One poster showed that reduced-doses of Velcade, cyclophosphamide (Cytoxan), and dexa­meth­a­sone are safe and effective for older, frail newly diag­nosed or refractory myeloma patients (abstract).  Overall, 91 per­cent of patients responded to the Velcade-based ther­apy.  Overall survival was 81 per­cent at one year, 63 per­cent at two years, and 46 per­cent at three years.  The researchers state that these results are similar to those seen for this com­bi­na­tion using standard doses; how­ever, side effects were less common with the reduced-dose regi­men.

Another study showed that Velcade-based ther­apy is effective after treat­ment with Kyprolis (abstract).  Overall, 81 per­cent of patients pre­vi­ously treated with Kyprolis later responded to Velcade-based ther­apy, in­clud­ing those who had also been treated with Velcade prior to Kyprolis ther­apy and those who were resistant to Kyprolis ther­apy.

Another poster summarized results of a study that in­ves­ti­gated the efficacy of adding clarithromycin to Revlimid plus dexa­meth­a­sone ther­apy for myeloma patients who progressed on the two-drug com­bi­na­tion (abstract).  Overall, 42 per­cent of patients responded to the three-drug com­bi­na­tion; patients who initially responded to Revlimid plus dexa­meth­a­sone were more likely to respond when clarithromycin was added com­pared to those who did not initially respond to the two-drug com­bi­na­tion (60 per­cent versus 29 per­cent).  The median pro­gres­sion-free survival was four months, and the median over­all survival was 25 months.

Another poster presented results from an analysis of second cancers among myeloma patients treated with Revlimid (abstract).  Half of the patients received Revlimid ther­apy as part of their initial treat­ment, trans­plant-eligible patients underwent stem cell trans­plan­ta­tion, and half of the patients received Revlimid main­te­nance ther­apy.  Among the 2,371 patients in­cluded in the study, 0.7 per­cent devel­oped a second cancer within a median follow-up time of 1.36 years from the start of treat­ment.  About half (47 per­cent) of the patients who devel­oped a second cancer received Revlimid as part of their treat­ment.  The researchers there­fore conclude that their data do not con­firm pre­vi­ous findings that Revlimid and stem cell trans­plan­ta­tion in­crease a patient’s risk of devel­op­ing a second cancer.

Posters About New Myeloma Treatments

As pre­vi­ously highlighted in The Beacon’s ASH Previews, a number of poster presentations are being made at ASH about results from clin­i­cal and pre­clin­i­cal studies of new drugs being devel­oped for the treat­ment of multiple myeloma.

Yesterday evening’s poster session in­cluded presentations about filanesib (ARRY-520), AT7519M, Cialis (tadalafil), daratumumab, FV-162, ixazomib (MLN9708), KW-2478, NOX-A12, panobinostat, quisinostat, ricolinostat (ACY-1215), selinexor (KPT-330), SNS01-T, TH-302, tivantinib (ARQ197), veliparib, and myeloma vaccines called ImMucin and Prevnar.

A number of these drugs look very promising.

One of the posters summarized initial findings from an ongoing Phase 1/2 trial investigating dara­tu­mu­mab in com­bi­na­tion with Revlimid and dex­a­meth­a­sone in re­lapsed and refractory multiple myeloma patients (abstract, full poster [PDF]).  Of the 11 patients evaluable for response, 73 per­cent have so far responded to the three-drug treat­ment. Depth of re­sponse also has been promising, with 46 per­cent of the patients achieving a very good partial re­sponse or com­plete re­sponse. According to the investigators, these results merit further clin­i­cal devel­op­ment of the three-drug com­bi­na­tion.

Another poster from the session presented results from a Phase 1/2 study of panobinostat plus Kyprolis (abstract).  Among the 44 re­lapsed and refractory patients enrolled in the study, nearly two-thirds (64 per­cent) of the patients responded.  The one-year pro­gres­sion-free survival rate was 41 per­cent, and the one-year over­all survival rate was 85 per­cent.

One of the posters presented results from a Phase 2a study of NOX-A12 in com­bi­na­tion with Velcade and dexa­meth­a­sone for re­lapsed myeloma (abstract).  Among the nine patients eval­u­ated for response so far, 67 per­cent responded to the com­bi­na­tion.

Results were also presented from a Phase 1/2 study of KW-2478 plus Velcade for the treat­ment of re­lapsed and refractory myeloma (abstract).  Among the 79 patients from Phase 2 of the study who were eval­u­ated for response, 38 per­cent responded.  Median pro­gres­sion-free survival was 7 months.

Another poster presented updated results from a Phase 1 study of veliparib in com­bi­na­tion with Velcade and dexa­meth­a­sone in re­lapsed and refractory myeloma patients (abstract).  Of the 18 patients eval­u­ated for response, 39 per­cent of patients responded.  The median pro­gres­sion-free survival was 5 months, and 71 per­cent were alive at 18 months.

A poster presenting results from a Phase 1/2 study showed that AT7519M is active when admin­istered in com­bi­na­tion with Velcade (abstract; full poster [PDF]).  Among the nine re­lapsed and refractory patients treated in Phase 2 of the study, 33 per­cent responded to the com­bi­na­tion.

One of the posters presented yesterday summarized initial findings of a Phase 1 trial of filanesib in com­bi­na­tion with Velcade (and, in many cases, dex­a­meth­a­sone) in re­lapsed and refractory multiple myeloma patients (abstract; full poster [PDF]). So far, 28 patients have been treated with varying doses of filanesib and Velcade.  The over­all re­sponse rate at the higher doses of filanesib was about 42 per­cent.

Initial results were also presented for a Phase 2 study of newly diag­nosed myeloma patients who underwent stem cell trans­plan­ta­tion and then received ixazomib plus Revlimid as main­te­nance ther­apy (abstract). Among 20 patients enrolled in the study, three have dis­con­tinued main­te­nance ther­apy and the rest have remained on ther­apy for up to 11 cycles. According to the investigators, the com­bi­na­tion seems to be well tol­er­ated.

Another ixazomib-related poster summarized results of a trial investigating the drug as a single agent in re­lapsed myeloma patients who are not resistant to treat­ment with Velcade (abstract).  This trial in­cluded 32 patients who were initially treated with only ixazomib; 63 per­cent of the patients had dex­a­meth­a­sone added to their treat­ment due to minimal re­sponse to ixazomib alone or disease pro­gres­sion.  Thus far, the over­all re­sponse rate has been 16 per­cent among patients treated with ixazomib alone, and 34 per­cent in those treated with both ixazomib and dex­a­meth­a­sone.

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Myeloma presentations from Day 2, Day 3, and Day 4 of the ASH 2013 meeting also will be summarized in ASH daily updates to be published at The Beacon the next few days.  Additional coverage of key research results from the meeting will con­tinue through­out the rest of the week 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.