A poster session yesterday at the 2015 American Society of Clinical Oncology (ASCO) annual meeting was the venue for the first substantial dose of multiple myeloma-related presentations at the conference.

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 posters were displayed throughout a large conference hall.

Most of the myeloma-related posters at the session focused on research related to either cur­rently approved myeloma ther­a­pies or potential new myeloma treat­ments.

This ASCO 2015 update from The Beacon will focus on research at yesterday’s session related to thera­pies cur­rently approved in the United States for the treat­ment of multiple myeloma.  In addi­tion, the update in­cludes at the end a review of several posters that summarized research about the impact of the del(17p) and t(11;14) chro­mo­som­al ab­nor­mal­i­ties on the prognosis of myeloma patients.

A second ASCO 2015 update to be published later will summarize the research about potential new myeloma ther­a­pies that was presented during the poster session.

Kyprolis

Two posters at yesterday’s session summarized important findings from studies related to Kyprolis (car­filz­omib).  Kyprolis is in the proteasome inhibitor class of myeloma ther­a­pies, which also includes Vel­cade (bor­tez­o­mib).  Kyprolis is approved in the United States for the treat­ment of re­lapsed myeloma. Amgen, the com­pany that markets Kyprolis, early this year filed for approval of the drug in Europe.

One of the Kyprolis-related posters yesterday summarized results of the Phase 1/2 CHAMPION-1 trial, which is evaluating the safety and efficacy of weekly high-dose Kyprolis com­bined with dex­a­meth­a­sone (Decadron) in patients with re­lapsed and refractory multiple myeloma (abstract #8527). The results included in the poster were for the 104 patients in the study who were treated at the maximum tolerated dose established during the Phase 1 portion of the trial.

The Kyprolis dosing in the trial was 20 mg/m² for the first infusion, then 70 mg/m² per infusion there­after. Infusions were once a week for three out of four weeks. The cur­rently approved Kyprolis dos­ing in the U.S. is 20 mg/m² per infusion for the first cycle and then 27 mg/m² thereafter, with infusions being done twice per week of treat­ment, instead of once per week as in the CHAMPION-1 trial.

Trial participants had a me­di­an of one pre­vi­ous ther­apy, but could have up to three prior ther­a­pies; 82 per­cent of the patients were pre­vi­ously treated with Vel­cade, and half were pre­vi­ously treated with Revlimid.

More than three quarters of the patients in the study responded to treat­ment (77 per­cent), and the me­di­an pro­gres­sion-free survival was 10.6 months. Hardly any patients experienced periph­eral neu­rop­athy as a result of treat­ment, and other side effects were mainly mild reductions in blood counts or fatigue, nausea, headaches, or diarrhea. There were, however, four deaths during the trial that were not due to disease pro­gres­sion, and more than 20 per­cent of the trial participants halted treat­ment either due to patient or physician choice.

Based in part on the results of the CHAMPION-1 trial, Amgen announced on Sunday that it is initiating a new global Phase 3 clinical trial known as the ARROW study.  The new trial will compare once-weekly high-dose Kyprolis com­bined with dex­a­meth­a­sone to twice-weekly standard-dose Kyprolis com­bined with dex­a­meth­a­sone (see related Amgen press release).

The second Kyprolis-related poster summarized results of a secondary analysis of data from the ASPIRE trial, which compares treat­ment with Kyprolis, Revlimid (lena­lido­mide), and dex­a­meth­a­sone (KRd) to treat­ment with Revlimid and dex­a­meth­a­sone (Rd) alone in patients with re­lapsed myeloma (abstract #8525). Data from the ASPIRE trial are the basis for Amgen’s application to have Kyprolis approved in Europe.

Patients in ASPIRE study had one to three prior lines of ther­apy, and were permitted to have been treated with Vel­cade (two thirds of the patients) and – with some limitations – Revlimid (20 per­cent of the patients). A summary of the key ASPIRE trial results can be found in this Beacon article reporting on Dr. Keith Stewart’s presentation of the study results at last year’s American Society of Hematology annual meeting.

The addi­tional analysis of the ASPIRE results focused on treat­ment out­comes by pre­vi­ous line of ther­a­py. The analysis finds show that use of the KRd regi­men after first relapse was asso­ci­ated with a one-year improvement in me­di­an pro­gres­sion-free survival (29.6 months for KRd versus 17.6 months for Rd).

In patients with two or more prior lines of ther­apy, KRd was asso­ci­ated with a nine-month improvement in me­di­an pro­gres­sion-free survival (25.8 months for KRd versus 16.7 months for Rd).

Revlimid

Another set of two posters at yesterday’s session presented updated results of important trials involving Revlimid. The drug is one of three cur­rently marketed myeloma ther­a­pies known as im­mu­no­mod­u­la­tory agents; the other two are thalidomide (Thalomid) and Pomalyst (poma­lido­mide, Imnovid).

The first Revlimid poster summarized the latest results from the so-called CALGB trial, which is one of three large trials that have been investigating Revlimid main­te­nance ther­apy after initial treat­ment for multiple myeloma (abstract #8523; poster [PDF] courtesy of Dr. Sarah Holstein). All three trials have shown that Revlimid main­te­nance delays disease pro­gres­sion. Only the CALGB trial, however, has shown an over­all survival benefit to Revlimid main­te­nance ther­apy (this Beacon news article summarizes the initial results of the three trials; the Beacon’s maintenance ther­apy topic page has other articles on the topic).

Patients in the CALGB trial were ran­domized to receive either Revlimid main­te­nance ther­apy or a placebo after they had undergone a stem cell trans­plant.

At a me­di­an follow-up time of 65 months, Revlimid main­te­nance con­tinues to dem­onstrate both significantly improved time to pro­gres­sion from the time of tran­splan­ta­tion (53 months versus 27 months) and improved over­all survival from the time of tran­splan­ta­tion (not yet reached versus 76 months) compared to placebo.

The researchers also find that Revlimid improved time to pro­gres­sion and over­all survival even in patients who had reached complete response before starting main­te­nance ther­apy.  The over­all survival benefit of Revlimid main­te­nance ther­apy was not as strong, however, in patients who had not received Revlimid as part of their initial myeloma ther­apy prior to their stem cell trans­plant.

The second Revlimid-related poster provided an updated look at results of the FIRST trial (abstract #8524).  The trial involves newly diagnosed, trans­plant-ineligible myeloma patients, and it compares continuous Revlimid and low-dose dex­a­meth­a­sone treat­ment to two alter­na­tive ther­a­pies: fixed-duration Revlimid and low-dose dex­a­meth­a­sone; and fixed-duration mel­phalan, pred­ni­sone, and thalido­mide (MPT).

The results show that, with a me­di­an follow-up time of 45 months, continuous Rd con­tinues to be asso­ci­ated with an over­all survival benefit compared to fixed duration Revlimid and low-dose dex­a­meth­a­sone and fixed-duration MPT (58.9 months versus 56.7 and 48.5 months, respectively).

The results also show that continuous Revlimid maintained its benefit as reflected in a metric known as “PFS2,” which measures the time from the start of treat­ment to when a patient experiences their second pro­gres­sion. PFS2 amounted to 42.9 months with continuous Revlimid, 40 months with fixed duration Revlimid, and 35 months with fixed-duration MPT.

Farydak

Two addi­tional posters during yesterday’s sessions looked at trial results involving Farydak (panobinostat), a new treat­ment for multiple myeloma that was approved by the U.S. Food and Drug Administration in Feb­ru­ary (see related Beacon news article).  Farydak’s approval is for use in re­lapsed myeloma patients in com­bi­na­tion with Vel­cade and dex­a­meth­a­sone. Novartis, the com­pany that markets Farydak, also has filed applications requesting approval of Farydak in Europe and Japan.

One poster yesterday reported results of a small Phase 2 trial examining the use of Farydak in com­bi­na­tion with Revlimid and dex­a­meth­a­sone in re­lapsed myeloma patients (abstract #8528; poster [PDF] courtesy of Dr. Ajai Chari). This study is of particular interest because Farydak is believed to work best in com­bi­na­tion with proteasome inhibitors such as Vel­cade, rather than im­mu­no­mod­u­la­tory agents such as Revlimid.

The Phase 2 study thus far has results for 20 myeloma patients with a me­di­an age of 64 and with a me­di­an of three prior myeloma ther­a­pies. All 20 patients had pre­vi­ously been treated with Revlimid, and three quarters of the patients had stopped responding to (were refractory to) Revlimid.  A third of the patients also had been treated with Pomalyst.

Overall, 45 per­cent of patients had at least a partial response to the Farydak, Revlimid, and dex­a­meth­a­sone regi­men.  The me­di­an pro­gres­sion-free survival was 6.5 months. The most common side effects were blood count-related – low white blood cell counts (55 per­cent) and low platelet counts (40 per­cent). The researchers did not observe any significant gastro­in­tes­ti­nal side effects, which had been reported in trials testing Farydak in com­bi­na­tion with Vel­cade and dex­a­meth­a­sone.

A second poster summarized the findings of a planned subanalysis of the PANORAMA-1 trial (abstract #8526).  The trial, which compare treat­ment with Farydak, Vel­cade and dex­a­meth­a­sone to treat­ment with just Vel­cade and dex­a­meth­a­sone, is the basis for Farydak’s approval in the U.S. and its application for approval in Europe.

The results of the PANOMARA-1 subanalysis show that the addi­tion of Farydak increased response rates and prolonged pro­gres­sion-free survival in patients who had pre­vi­ously been treated with Vel­cade and an im­mu­no­mod­u­la­tory agent.

In the 25 per­cent of the trial patients who had pre­vi­ously been treated with Vel­cade and an im­mu­no­mod­u­la­tory agent, 59 per­cent of those who received Farydak, Vel­cade and dex­a­meth­a­sone responded, compared to 41 per­cent of patients who received Vel­cade and dex­a­meth­a­sone alone. Progression-free survival was 10.6 months for patients who received Farydak, Vel­cade and dex­a­meth­a­sone, compared to 5.8 months for patients who received Vel­cade and dex­a­meth­a­sone alone.

The researchers also found that Farydak’s safety profile in the patients pre­vi­ously treated with Vel­cade and im­mu­no­mod­u­la­tory agents was consistent with that seen in the over­all PANORAMA-1 patient population.

Del(17p) And T(11;14)

Three posters during yesterday’s poster session summarized findings about the impact of specific chro­mo­som­al ab­nor­mal­i­ties on the prognosis of newly diagnosed multiple myeloma patients.

One of these posters focused on the del(17p) chro­mo­som­al ab­nor­mal­i­ty, which is considered a high-risk chro­mo­som­al ab­nor­mal­i­ty asso­ci­ated with earlier relapse and shorter over­all survival (abstract #8582; poster [PDF] courtesy of Dr. Jatin Shah).  The analysis is based on data from 1,450 newly diagnosed multiple myeloma patients from treat­ment centers across the United States.  Patients in the study were diagnosed between September 2009 and December 2011.

The del(17p) ab­nor­mal­i­ty was present in seven per­cent of the patients in the study sample.  Patients with the ab­nor­mal­i­ty had shorter me­di­an over­all survival than the rest of the patients (38.6 months versus not yet reached).

Transplantation as part of first-line ther­apy seems to have been beneficial for del(17p) patients. Del(17p) patients who had an upfront trans­plant had longer me­di­an over­all survival than those who did not (not yet reached versus 31.3 months).  The beneficial impact of tran­splan­ta­tion was significant even when the researchers controlled for factors – such as patient age – which might have affected both survival and whether the patient was able to have a trans­plant.

Two other posters examined the impact of the t(11;14) chro­mo­som­al ab­nor­mal­i­ty in multiple myeloma. Patients with t(11;14) are typically considered to have standard-risk disease. However, a study published two years ago by MD Anderson researchers suggested that the t(11;14) ab­nor­mal­i­ty may have a negative impact on the prognosis of myeloma patients (see related Beacon news).

One study at yesterday’s poster session examined t(11;14) in newly diagnosed myeloma patients, regardless of whether or not they opted to have a trans­plant as part of their upfront ther­apy (abstract #8592; poster [PDF] courtesy of Dr. Muhamad Alhaj Moustafa). The analysis was based on data from 199 patients with t(11;14) who were seen at the Mayo Clinic and had FISH chro­mo­som­al ab­nor­mal­i­ty testing done within two years before or after their myeloma diag­nosis. Patients could be included in the study if their FISH testing was done between 2004 and 2012.

Median pro­gres­sion-free survival was 15 months across all 199 patients in the study, and me­di­an over­all survival was 68 months. Median over­all survival did not appear to change during the period covered by the study, and it was similar for patients receiving older, conventional chemotherapy agents and for patients who had at least one of the novel myeloma ther­a­pies (Revlimid or Vel­cade) (68 months versus 70.5 months).

Patients who received a stem cell trans­plant at some point after diag­nosis had significantly longer over­all survival than those who did not (72 months versus 35 months). The researchers did not report, however, whether the age of the trans­plant and non-transplant patients may have affected the observed difference in survival based on tran­splan­ta­tion.  (Older myeloma patients typically have shorter over­all survival than younger myeloma patients, and older patients also are less likely to undergo tran­splan­ta­tion.)

Patients in the study who had the del(17p) chro­mo­som­al ab­nor­mal­i­ty in addi­tion to the t(11;14) ab­nor­mal­i­ty had shorter me­di­an over­all survival than those who did not have the del(17p) ab­nor­mal­i­ty (26 months versus 73 months).

The second study that focused on t(11;14) also involved patients seen at the Mayo Clinic.  However, all patients in the second study underwent stem cell tran­splan­ta­tion within a year of their myeloma diag­nosis (abstract #8583; poster [PDF] courtesy of Dr. Greg Kaufman). The analysis is based on data from 409 newly diagnosed multiple myeloma patients who were diagnosed between 2003 and 2012. This sample includes patients with t(11;14) and patients with other chro­mo­som­al ab­nor­mal­i­ties, including no chro­mo­som­al ab­nor­mal­i­ties at all.

The researchers found that patients with the t(11;14) ab­nor­mal­i­ty had shorter pro­gres­sion-free survival (28.1 months versus 30.4 months) and shorter over­all survival (73.4 months versus 103 months) than other patients considered to have standard-risk disease. However, pro­gres­sion-free survival (28.1 months versus 24.9 months) and over­all survival (73.4 months versus 60.5 months) for t(11;14) patients were longer compared to patients classified as having high-risk disease. The researchers believe their results call into question the current classification of myeloma patients with the t(11;14) ab­nor­mal­i­ty as standard-risk patients.

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For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2015 coverage. In addi­tion, The Beacon has complete lists of all ASCO 2015 myeloma-related oral presentations, poster presentations, education session presentations, and e-abstracts.