The main mul­ti­ple myeloma-related poster session at this year's Amer­i­can Society of Clinical Oncology (ASCO) annual meeting in Chicago took place last Monday. Several of the posters pre­sented during that session focused on poten­tial new mul­ti­ple myeloma ther­a­pies. Those posters were reviewed in the Beacon's previous ASCO mul­ti­ple myeloma up­date.

In this, the Beacon's final ASCO 2016 up­date, the attention shifts to posters from the Monday session that were re­lated to existing myeloma ther­a­pies, as well as a pair of posters re­lated to smol­der­ing mul­ti­ple myeloma.

The posters about existing ther­a­pies con­cern Empliciti (elo­tuzu­mab), Ninlaro (ix­az­o­mib), Pomalyst (poma­lido­mide, Imnovid), and Kyprolis (car­filz­o­mib).

The Empliciti and Ninlaro posters explore in more detail how well each of the drugs work in cer­tain subgroups of patients. The posters sug­gest that both drugs are well suited for patients with high-risk chromosomal ab­nor­mal­i­ties. In addi­tion, the Ninlaro re­search sug­gests that the drug can be ef­fec­tive in patients who pre­vi­ously have been treated with Velcade (bor­tez­o­mib).

The Pomalyst and Kyprolis posters provide addi­tional insights into the  safety of Pomalyst in heavily pre­treated patients, and the ef­fec­tiveness of Kyprolis in patients who pre­vi­ously re­lapsed soon after initial treat­ment.

The smol­der­ing myeloma posters are about two topics: first, identifying smol­der­ing patients with a high risk of early pro­gres­sion to symp­tomatic dis­ease by counting myeloma cells in patient blood samples; and, sec­ond, estab­lishing how many newly diag­nosed smol­der­ing myeloma patients there are in comparison to the num­ber of newly diag­nosed patients with symp­tomatic mul­ti­ple myeloma.

A Couple Of Reminders (For Those New To These Updates)

As was the case with the Beacon's pre­vi­ous ASCO up­dates, this article in­cludes links to actual posters pre­sented at the meeting (when they are avail­able). Addi­tional links will be added in the com­ing weeks.

Readers also are reminded that the Beacon has compiled lists of all ASCO 2016 mul­ti­ple myeloma-related oral pre­sen­ta­tions, poster pre­sentations, education session pre­sen­ta­tions, and e-abstracts. The lists in­clude pre­sen­ta­tion titles, authors, and links to each pre­sen­ta­tion's abstract and the re­lated slides or poster (when avail­able). Links to these pages with these lists cur­rently can be found near the top of the Beacon's sidebar, on the right side of every Beacon page.

Empliciti – Updated ELOQUENT-2 Subgroup Analyses

One poster from last Monday's session summarized new re­­sults from an im­por­tant Empliciti clin­i­cal trial. The ELOQUENT-2 trial com­pared treat­ment with Empliciti, Revlimid (lena­lido­mide), and dexa­meth­a­sone to treat­ment with Revlimid and dexa­meth­a­sone alone. Patients in the trial had re­lapsed mul­ti­ple myeloma with one to three prior lines of ther­apy.

Results of the ELOQUENT-2 trial were the basis for last year's U.S. Food and Drug Admin­istra­tion (FDA) ap­prov­al of Empliciti as a new treat­ment for mul­ti­ple myeloma.

The new ELOQUENT-2 re­­sults pre­sented at last week's ASCO poster session are an up­dated and ex­panded “subset analysis”, or report of key trial re­­sults for spe­cif­ic subgroups of patients.

In par­tic­u­lar, the new analysis looks at pro­gres­sion-free sur­vival, over­all sur­vival, duration of re­sponse, and over­all re­sponse rate for subgroups of patients.

The subgroups are defined by factors such as a patient's risk classification at the start of the trial, whether a patient was resistant (refractory) to their last myeloma ther­apy, whether a patient had a del(17p) or t(4;14) chromosomal ab­nor­mal­ity at the start of the trial, and whether a patient had pre­vi­ously been treated with Velcade or Revlimid (abstract).

The re­­sults of the analysis are more extensive – and up­dated – in comparison to the subgroup analysis of pro­gres­sion-free sur­vival in­cluded in the pub­lished re­­sults of the ELOQUENT-2 trial (full text).

The re­­sults pre­sented last Monday in­di­cate that adding Empliciti to Revlimid and dexa­meth­a­sone ther­apy im­proves treat­ment out­comes in all the analyzed patient subgroups.

The subgroup analysis focused on over­all sur­vival out­comes, how­ever, sug­gests that adding Empliciti was par­tic­u­larly beneficial to patients who had the del(17p) or t(4;14) chromosomal ab­nor­mal­ity, patients who had high-risk dis­ease in general, and patients who had be­come resistant (refractory) to the last treat­ment they had before entering the trial.

For example, among patients with the t(4;14) chromosomal ab­nor­mal­ity, median over­all sur­vival was 16 months longer for patients who re­ceived treat­ment with Empliciti, Revlimid, and dexa­meth­a­sone com­pared to those who re­ceived treat­ment with just Revlimid and dexa­meth­a­sone.

Ninlaro – New Analyses Of TOURMALINE-MM1 Trial Outcomes

Two posters at last Monday’s session pre­sented new analyses of data from the TOURMALINE-MM1 clin­i­cal trial. The re­­sults of this trial were the basis for last year’s FDA ap­prov­al of Ninlaro as a new treat­ment for mul­ti­ple myeloma.

Ninlaro is an orally admin­istered drug in the pro­te­a­some in­hib­i­tor class of ther­a­pies, which also in­cludes Velcade and Kyprolis. Ninlaro is chemically similar to Velcade, but it is nonetheless a dif­fer­en­t drug – much as Revlimid is chemically similar to thalido­mide, but is still a dif­fer­en­t drug.

Patients in the TOURMALINE-MM1 trial had re­lapsed or re­frac­tory mul­ti­ple myeloma and one to three prior lines of ther­apy. Each trial par­tic­i­pant was ran­domly assigned to re­ceive treat­ment with either Ninlaro, Revlimid, and dexa­meth­a­sone, or a placebo capsule, Revlimid, and dexa­meth­a­sone.

The Impact Of High-Risk Chromosomal Abnormalities

One of the TOURMALINE-MM1 posters reported on the im­pact of high-risk chromosomal ab­nor­mal­i­ties on treat­ment out­comes among the trial par­tic­i­pants (abstract, poster [PDF]). The study authors defined high-risk chromosomal ab­nor­mal­i­ties to in­clude del(17p), t(4;14), and t(14;16).

Among patients in the trial who had one or more high-risk chromosomal ab­nor­mal­i­ties, treat­ment with Ninlaro, Revlimid, and dexa­meth­a­sone led to a higher over­all re­sponse rate (79 per­cent) than treat­ment with placebo, Revlimid, and dexa­meth­a­sone (60 per­cent).

In fact, patients with no high-risk chromosomal ab­nor­mal­i­ties who were treated with Ninlaro, Revlimid, and dexa­meth­a­sone had only a slightly higher over­all re­sponse rate (80 per­cent) than the high-risk patients treated with the same regi­men.

High risk patients also were more likely to achieve a deeper re­sponse if they were treated with the Ninlaro-containing regi­men. Forty five per­cent of the high-risk patients treated with Ninlaro, Revlimid, and dexa­meth­a­sone had at least a very good partial re­sponse to treat­ment, com­pared to 21 per­cent of the patients who re­ceived treat­ment with the placebo, Revlimid, and dexa­meth­a­sone.

The broader and deeper re­sponses seen among the high-risk patients treated with Ninlaro, Revlimid, and dexa­meth­a­sone translated into a pro­gres­sion-free sur­vival ben­e­fit.

Median pro­gres­sion free sur­vival was almost a year longer in the high-risk patients treated with Ninlaro, Revlimid, and dexa­meth­a­sone than in the patients who re­ceived the placebo, Revlimid, and dexa­meth­a­sone (21.4 months versus 9.7 months, re­spec­tive­ly).

The study authors did not con­duct any analyses of over­all sur­vival out­comes. Those re­­sults, they noted, “were not mature.”

The Impact Of Prior Therapies

The other TOURMALINE-MM1 poster reported on the im­pact of prior ther­apy on treat­ment out­comes (abstract, poster [PDF]). In par­tic­u­lar, prior exposure to Velcade, thalido­mide, and Revlimid was examined.

Patients were permitted to par­tic­i­pate in the TOURMALINE-MM1 trial if they had pre­vi­ously been treated with either Revlimid, thalido­mide, or a pro­te­a­some in­hib­i­tor such as Velcade or Kyprolis. Patients could not par­tic­i­pate in the trial, how­ever, if their dis­ease had at some point be­come resistant (refractory) to either Revlimid or a pro­te­a­some in­hib­i­tor.

As it turns out, more than two thirds of the TOURMALINE-MM1 trial par­tic­i­pants (70 per­cent) were pre­vi­ously treated with a pro­te­a­some in­hib­i­tor, which in almost all cases was Velcade. Also, more than half the patients (55 per­cent) had pre­vi­ously been treated with either Revlimid or thalido­mide, although in most of these cases the pre­vi­ous treat­ment was thalido­mide (45 per­cent) rather than Revlimid (12 per­cent).

Prior exposure to either Velcade, Revlimid, or thalido­mide did reduce somewhat how many patients responded to the Ninlaro, Revlimid, and dexa­meth­a­sone treat­ment regi­men, and it also reduced depth of re­sponse to that regi­men.

Nevertheless, even in patients pre­vi­ously exposed to Velcade, Revlimid, or thalido­mide, treat­ment with Ninlaro, Revlimid, and dexa­meth­a­sone yielded more re­sponses – and deeper re­sponses – than treat­ment with the placebo, Revlimid, and dexa­meth­a­sone.

For example, in patients pre­vi­ously treated with a pro­te­a­some in­hib­i­tor, the over­all re­sponse rate in patients treated with Ninlaro, Revlimid, and dexa­meth­a­sone was about 75 per­cent, and the share of patients achieving at least a very good partial re­sponse was 46 per­cent. In patients treated with the placebo, Revlimid, and dexa­meth­a­sone, the over­all re­sponse rate was about 70 per­cent, and the share of patients reaching at least a very good partial re­sponse was 40 per­cent.

Perhaps more im­por­tantly, adding Ninlaro to Revlimid and dexa­meth­a­sone ther­apy im­proved pro­gres­sion-free sur­vival con­sis­tently re­gard­less of whether or not patients were pre­vi­ously treated with Velcade.

In patients who had never been treated with Velcade, adding Ninlaro to Revlimid, and dexa­meth­a­sone reduced the rate at which patients ex­peri­enced dis­ease pro­gres­sion or death by 25.3 per­cent.

The re­duc­tion was almost exactly the same – 25.4 per­cent – in patients who had pre­vi­ously been treated with Velcade.

Based on their findings, the study authors conclude that patients who pre­vi­ously have been treated with Velcade, Revlimid, or thalido­mide should still be con­sidered for treat­ment with Ninlaro in com­bi­na­tion with Revlimid and dexa­meth­a­sone.

Pomalyst – Safety Analysis Based On Data From Three Clinical Trials

One poster last Monday pre­sented an analysis of the safety of Pomalyst com­bined with dexa­meth­a­sone, using data from three clin­i­cal trials (abstract).

The 1,088 patients who re­ceived Pomalyst and dexa­meth­a­sone in the three trials were generally heavily pre­treated. They could only par­tic­i­pate in the trials if they pre­vi­ously had been treated with Revlimid and Velcade, and they had to have a min­i­mum of 2 prior lines of ther­apy.

The patients re­ceived Pomalyst 4 mg for 21 days out of 28-day cycle, and 40 mg of dexa­meth­a­sone weekly.

The most common severe (Grade 3 or 4) side effects observed in the patients were neu­tro­penia (56 per­cent), in­fec­tions (34 per­cent), anemia (32 per­cent), and low platelet levels (thrombocytopenia) (26 per­cent). Over­all, 2 per­cent of patients ex­peri­enced severe venous thrombo­embolic (blood clot-related) events, and 1 per­cent ex­peri­enced severe periph­eral neu­rop­athy.

Just under a quarter of the patients (24 per­cent) re­quired Pomalyst dose re­duc­tions, and 66 per­cent re­quired dose inter­rup­tions, due to side effects. Seven per­cent of the patients dis­con­tinued treat­ment due to side effects.

Kyprolis – Impact Of Treatment In Early Relapsers

One poster during Monday’s poster session in­ves­ti­gated the im­pact of adding Kyprolis to Revlimid-dexamethasone ther­apy in patients who re­lapsed early after their first myeloma ther­apy, or after their first stem cell trans­plant (abstract).

The re­­sults are based on a sec­ond­ary analysis of data from the Phase 3 ASPIRE clin­i­cal trial, which in­ves­ti­gated the ef­fi­cacy and safety of Kyprolis plus Revlimid and dexa­meth­a­sone in re­lapsed and re­frac­tory mul­ti­ple myeloma patients.

Patients in the trial had one to three prior lines of ther­apy. Half the patients were ran­domly selected to be treated with Kyprolis, Revlimid, and dexa­meth­a­sone, while the other half were treated with just Revlimid and dexa­meth­a­sone.

The sec­ond­ary analysis in­cluded data from 159 patients who re­lapsed one year or less from the time they started the first line of prior ther­apy and 97 patients who re­lapsed one year or less after their first prior trans­plant.

The over­all re­sponse rate was 79 per­cent for patients who re­lapsed early and re­ceived Kyprolis, Revlimid, and dexa­meth­a­sone com­pared to 61 per­cent for patients who re­lapsed early and re­ceived Revlimid and dexa­meth­a­sone.  Median pro­gres­sion-free sur­vival was 24.1 months for patients who re­lapsed early and re­ceived Kyprolis, Revlimid, and dexa­meth­a­sone, com­pared to 12.5 months for patients who re­lapsed early and re­ceived Revlimid and dexa­meth­a­sone

Similar re­­sults were seen in patients who re­lapsed one year or less after their first prior trans­plant. The over­all re­sponse rate was 83 per­cent for patients who re­ceived Kyprolis, Revlimid, and dexa­meth­a­sone com­pared to 61 per­cent of patients who re­ceived for Revlimid-dexamethasone.  Median pro­gres­sion-free sur­vival was 17.3 months for patients re­ceiv­ing Kyprolis, Revlimid, and dexa­meth­a­sone versus 11.1 months for patients re­ceiv­ing Revlimid and dexa­meth­a­sone.

Smoldering Multiple Myeloma

There were two posters re­lated to smol­der­ing mul­ti­ple myeloma at last Monday’s poster session. Both were by re­searchers at the Mayo Clinic.

Myeloma Cells In The Blood And Risk Of Progression

The first poster examined a poten­tial new way of identifying smol­der­ing myeloma patients with a high risk of pro­gress­ing to symp­tomatic dis­ease re­quir­ing treat­ment.

In par­tic­u­lar, the re­searchers explored whether the num­ber of myeloma cells ("clonal plasma cells") in a smol­der­ing myeloma patient’s blood is re­lated to risk of pro­gres­sion (abstract, poster [PDF] courtesy of Dr. Wilson Gonsalves).

The re­searchers analyzed blood samples for 100 smol­der­ing mul­ti­ple myeloma patients who were seen at their treat­ment center be­tween Jan­u­ary 2008 and De­cem­ber 2013. In par­tic­u­lar, they used six-color multiparametric flow cytometry (MFC) to analyze 150,000 cells from each patient’s blood sample and de­ter­mine the num­ber of myeloma cells among all the cells analyzed.

The found that patients with a higher num­ber of myeloma cells in the blood were more likely to progress to symp­tomatic dis­ease within the next two years. A cutoff of 150 myeloma cells was found to be the best for dif­fer­en­tiating be­tween patients at high-risk for early pro­gres­sion and those at lower risk.

Patients who had more than 150 myeloma cells in their blood sample were much more likely to progress to symp­tomatic dis­ease within a short period of time. Median time to pro­gres­sion for these patients was 10 months. For the rest of the patients, median time to pro­gres­sion has not yet been reached, but is likely to be well over five years.

Prevalence Of Smoldering Multiple Myeloma

The sec­ond smol­der­ing myeloma poster (abstract; poster [PDF] courtesy of Aishwarya Ravindran) focuses on a question that not many people realize has yet to be answered accurately. The question is: How many people are diag­nosed with smol­der­ing mul­ti­ple myeloma every year?

There is not yet a good answer to this question because there is not yet a spe­cif­ic “diagnostic code” for tracking diagnoses of smol­der­ing mul­ti­ple myeloma separate from diagnoses of symp­tomatic (active) mul­ti­ple myeloma. Instead, there is just one diagnostic code for “multiple myeloma.”

The authors of the cur­rent study there­fore turned to the National Cancer Data Base, which has rel­a­tively detailed in­­for­ma­tion for about 70 per­cent of all new cancer cases in the United States.

Working with in­­for­ma­tion in the database for the period 2003 to 2011, the re­searchers esti­mated the share of newly diag­nosed “multiple myeloma” patients who had either active mul­ti­ple myeloma or smol­der­ing mul­ti­ple myeloma. They also created an “unknown” category for cases where they could not be sure if a patient had active or smol­der­ing dis­ease.

Among the 86,327 mul­ti­ple myeloma diagnoses in the database, the re­searchers esti­mated that 13.7 per­cent were initially diag­nosed with smol­der­ing mul­ti­ple myeloma patients, 80.6 per­cent were initially diag­nosed with active (symptomatic) mul­ti­ple myeloma patients, and 5.7 per­cent were "unknown."

Previous stud­ies at spe­cif­ic in­sti­tu­tions had esti­mated that smol­der­ing myeloma was be­tween 8 and 20 per­cent of all newly diag­nosed "multiple myeloma" cases.