Yesterday was the second day of the American Society of Hematology’s (ASH) annual meeting, which is being held in New Orleans.

As on Saturday, myeloma-related presentations were once again made during several sessions throughout the day.

Experts who missed the education session on Saturday had the opportunity to attend the session again early Sunday morning.

One myeloma study was presented during the plenary session in the early afternoon. The six presentations in this session covered all blood cancers and are considered particularly important studies.

The myeloma study included in this session was a Phase 3 trial comparing Revlimid (lena­lido­mide) plus dexamethasone (Decadron) to melphalan (Alkeran) plus prednisone and thalidomide (Thalomid) in newly diagnosed multiple myeloma patients who are 65 years and older or not eligible for a stem cell trans­plant. This trial may ultimately lead to the approval of Revlimid as frontline ther­apy in this patient population.

Two sessions of oral myeloma-related presentations ran simultaneously in the late afternoon. One of the sessions focused on the biology of the disease; the other one included presentations on pre-clinical studies investigating predictive markers of myeloma biology.

The bulk of myeloma-related research was once again presented during a poster session in the evening, where important new research findings were summarized in posters displayed throughout a large conference hall.

Myeloma Presentation In Plenary Session

The myeloma trial featured in the plenary session was a multi-center Phase 3 trial comparing the efficacy and safety of Revlimid and dexa­meth­a­sone to that of mel­phalan plus pred­ni­sone and thalido­mide in newly diagnosed multiple myeloma patients who were 65 years and older or not eligible for stem cell trans­plan­ta­tion (abstract).  The results were presented by Dr. Thierry Facon from the Hospital Claude Huriez in Lille, France.

The study included 1,623 newly diagnosed multiple myeloma patients with a median age of 73 years.

Patients were divided into one of three treat­ment groups, receiving either Revlimid plus dexa­meth­a­sone (Rd) until disease pro­gres­sion, Rd for 72 weeks, or mel­phalan plus pred­ni­sone and thalido­mide (MPT) for 72 weeks.

The results showed that more patients responded to continuous treat­ment with Revlimid (75 per­cent) than 72 weeks of RD (73 per­cent) or MPT (62 per­cent).

The median pro­gres­sion-free survival was significantly longer for those who received continuous Rd (26 months) than for those who received Rd for 72 weeks (21 months) and those who received MPT (21 months).  The differences in pro­gres­sion-free survival became apparent right at the 72-week mark when two of the groups dis­con­tinued treat­ment.

Likewise, the four-year over­all survival was longest for those who received continuous Rd (59 per­cent), compared to those who received Rd for 72 weeks (56 per­cent) and those who received MPT (51 per­cent).  The difference was significant for continuous Rd compared to MPT.

MPT is cur­rently approved in Europe for the treat­ment of newly diagnosed multiple myeloma patients who are not can­di­dates for stem cell trans­plan­ta­tion. The results of this study may eventually lead to the approval of Revlimid as frontline ther­apy in this patient population in Europe.

Posters About Combination Therapies

During the poster session last night, there were several studies involving com­bi­na­tion ther­a­pies with Kyprolis (car­filz­o­mib) and Pomalyst (poma­lido­mide, Imnovid), the two most recently approved myeloma treat­ments.

One poster summarized the final results of a Phase 1/2 study of Kyprolis plus cyclophosphamide (Cytoxan), thalido­mide, and dexa­meth­a­sone – a com­bi­na­tion ther­apy known as “CYCLONE” – in newly diagnosed myeloma patients (abstract). According to the researchers, the com­bi­na­tion is highly efficacious; after four treat­ment cycles, 91 per­cent of patients responded, with 76 per­cent achieving at least a very good partial response. The two-year pro­gres­sion-free survival was 77 per­cent, and the two-year over­all survival was 98 per­cent.

Another poster summarized results of a study that in­ves­ti­gated the sequential approach of upfront Kyprolis plus dexa­meth­a­sone, followed by consolidation ther­apy with Revlimid, clarithromycin (Biaxin), and dexa­meth­a­sone, and finally Revlimid main­te­nance as first-line ther­apy for newly diagnosed myeloma patients (abstract). Overall, 83 per­cent of patients responded to Kyprolis-dexamethasone induction (9 per­cent stringent complete response, 39 per­cent very good partial response, and 35 per­cent partial response), which according to the researchers compares favorably to similar studies using Velcade (bor­tez­o­mib)-based com­bi­na­tions. The researchers point out that responses deepened with Revlimid consolidation and main­te­nance ther­apy (13 per­cent stringent complete response, 48 per­cent very good partial response, and 26 per­cent partial response).

There was also a poster that summarized the results of a side-by-side analysis of ran­domized Phase 2 and Phase 3 trials of Pomalyst plus low-dose dexa­meth­a­sone in patients with advanced myeloma who had pre­vi­ously received Revlimid and Velcade (abstract). The researchers found that in both studies Pomalyst plus low-dose dexa­meth­a­sone extended pro­gres­sion-free survival in advanced re­lapsed myeloma patients compared to Pomalyst alone or high-dose dexa­meth­a­sone alone. Response and survival rates were not negatively impacted by resistance (being refractory) to Revlimid or Velcade, even if it was their last prior ther­apy. Based on their findings, the researchers recommend that Pomalyst plus low-dose dexa­meth­a­sone should be considered a standard of care for patient with advanced myeloma who have become refractory to Revlimid and Velcade.

Findings from a sub-analysis were summarized in another poster showing that Pomalyst plus low-dose dexa­meth­a­sone is beneficial for re­lapsed and refractory myeloma patients over the age of 65 years (abstract). Patients who received Pomalyst plus low-dose dexa­meth­a­sone had higher response rates and longer pro­gres­sion-free and over­all survival than patients who received high-dose dexa­meth­a­sone. The investigators point out that the results for patients over the age of 65 were similar to those for patients aged 65 or younger. According to the investigators, their findings support considering Pomalyst plus low-dose dexa­meth­a­sone as a standard treat­ment option for re­lapsed and refractory myeloma patients regardless of age.

Another poster presented the results of a Phase 2 trial in which some of the patients were treated with Pomalyst plus dexa­meth­a­sone and some also had oral weekly cyclophosphamide added to their regi­men (abstract).  All patients were refractory to pre­vi­ous Revlimid ther­apy.  Of the 66 patients evaluable for response, 49 per­cent responded, with 2 per­cent achieving a complete response, 15 per­cent a very good partial response, and 32 per­cent a partial response.  The median pro­gres­sion-free survival was 6.4 months. According to the investigators, these results compare favorably to published results of Pomalyst and dexa­meth­a­sone in Revlimid-refractory myeloma patients.

Another Phase 2 trial compared continuous Pomalyst dosing (2 mg daily) to intermittent Pomalyst dosing (4 mg per day for 21 out of 28 days) in re­lapsed and refractory myeloma patients who had received a median of four prior ther­a­pies (abstract). The results showed that 21 per­cent in the continuous dosing group and 45 per­cent of patients in the intermittent dosing group responded to treat­ment. However, pro­gres­sion-free survival was similar between the two treat­ment groups (4.4 months for the continuous dosing group versus 5.1 months for the intermittent dosing group), and the median over­all survival was the same for both groups (18 months). Based on their findings, the researchers recommend the intermittent Pomalyst dosing for further testing in Phase 3 trials.

Another poster presented results of a Phase 1/2 trial of Pomalyst, dexa­meth­a­sone, and Doxil (doxo­ru­bi­cin liposomal) in re­lapsed and refractory myeloma patients who were refractory to Revlimid (abstract). Of the 32 patients evaluable for response, 31 per­cent of patients responded to treat­ment. Researchers observed high rates of low white blood cell counts at the initial 4 mg daily dose of Pomalyst. The Pomalyst dose was lowered to 3 mg, and no addi­tional cases of low white blood cell counts were observed.

Results of studies investigating treat­ment with Revlimid and Velcade were also displayed during yesterday’s poster session.

One poster summarized interim results of an ongoing clinical trial indicating that treat­ment with Revlimid and dexa­meth­a­sone alone is equally effective as treat­ment with Revlimid and dexa­meth­a­sone followed by stem cell trans­plan­ta­tion in newly diagnosed myeloma patients (abstract). Even though the addi­tion of stem cell trans­plan­ta­tion resulted in a trend toward improved over­all response rates (96 per­cent for patients undergoing stem cell trans­plan­ta­tion versus 77 per­cent for patients receiving Revlimid and dexa­meth­a­sone alone), it did not result in a significant difference in pro­gres­sion-free or over­all survival between the two treat­ment arms.

Another study showed that approx­i­mately one-fifth of newly diagnosed myeloma patients can achieve long-term responses (lasting more than three years) with Revlimid (abstract). These patients were more likely to have standard-risk disease and to have achieved at least a very good partial response with Revlimid. In addi­tion, long-term responders had a longer median time to best response, compared to patients who responded for less than three years.

Results of a retrospective analysis indicate that newly diagnosed myeloma patients can achieve com­parable out­comes with Velcade-cyclophosphamide-dexamethasone (VCD) and Velcade-Revlimid-dexamethasone (VRD) (abstract), which is significant given the substantial difference in treat­ment cost between the two regi­mens. Overall, 93 per­cent of patients responded to VCD and 87 per­cent responded to VRD. The two-year pro­gres­sion-free survival rates were 73 per­cent with VCD and 71 per­cent with VRD, and the two-year over­all survival rates were 91 per­cent and 87 per­cent, respectively.

Canadian researchers reported long-term survival data for newly diagnosed multiple myeloma patients who received induction ther­apy with Velcade, cyclophosphamide, and dexa­meth­a­sone, commonly referred to as CyBorD (abstract). Overall, 89 per­cent of patients responded to treat­ment, with 62 per­cent achieving a very good partial response or better.  The five-year pro­gres­sion-free survival was 42 per­cent, and the five-year over­all survival was 70 per­cent. Based on their findings, the Canadian researchers recommend that CyBorD induction should be considered a standard regi­men for newly diagnosed myeloma patients who are eligible for stem cell trans­plan­ta­tion.

Posters About New Myeloma Treatments

As mentioned in The Beacon’s ASH Previews published over the last couple of weeks, 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.

During last night’s poster presentation, results for IPH2101, LGH447, oprozomib, Reolysin, and ricolinostat (ACY-1215) were presented.

The most promising results are summarized below.

One poster showed the results for a Phase 1b study of ricolinostat in com­bi­na­tion with Revlimid and dexa­meth­a­sone (abstract). Among the 13 patients evaluated for response, 69 per­cent responded, with 8 per­cent achieving a complete response, 31 per­cent a very good partial response, 23 per­cent a partial response, and 8 per­cent an unconfirmed partial response.  Among the patients who were resistant to pre­vi­ous Revlimid ther­apy, 33 per­cent responded to the ricolinostat com­bi­na­tion ther­apy.

Results from a Phase 1 study of IPH2101 plus Revlimid in re­lapsed myeloma patients were also shown during last night’s poster session (abstract; full poster [PDF]). Overall, the response rate was 33 per­cent, with 13 per­cent of the patients achieving a very good partial response and 20 per­cent achieving a partial response; 20 per­cent of these patients had pre­vi­ously received Revlimid plus dexa­meth­a­sone.  The median duration of response was at least 20 months.

Researchers also presented interim results of an ongoing Phase 1b/2 clinical trial of oprozomib in patients with multiple myeloma and Waldenström’s macro­glob­uli­nemia (abstract). The study includes 42 re­lapsed patients (30 with multiple myeloma and 12 with Waldenström’s macro­glob­ulinemia) who were treated with oprozomib, using one of two different dosing schedules.  About one quarter (28 per­cent) of the myeloma patients in the one dosing group responded to treat­ment, with 11 per­cent achieving a very good partial response and 17 per­cent achieving a partial response; in the second dosing group, 13 per­cent of patients responded, half of which achieved a very good partial response and the other half a partial response.

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Myeloma presentations from 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 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.