This year’s meeting of the American Society of Clinical Oncology (ASCO) was held May 31 through June 4 in Chicago.

During the meeting, The Beacon pub­lished daily up­dates that provided over­views of the im­por­tant mul­ti­ple myeloma findings pre­sented during the meeting.

Now that the meeting has concluded, the focus shifts to the bigger picture: What were the key findings of the meeting? Were there re­­sults with im­medi­ate im­pli­ca­­tions for the treat­ment of mul­ti­ple myeloma?  Did the re­search at the meeting rep­re­sent a major step for­ward for myeloma patients, or was it more incremental in nature?

To address these questions, the Beacon Staff con­ducted its own in-depth review of the meeting’s re­search, and it also consulted with a num­ber of myeloma spe­cialists.

In par­tic­u­lar, The Beacon re­ceived feedback about the meeting from myeloma spe­cialists Dr. Amrita Krish­nan from City of Hope, Dr. Shaji Kumar from the Mayo Clinic, Dr. Paul Richardson from the Dana-Farber Cancer In­sti­tute, Dr. Frits van Rhee from the Myeloma In­sti­tute for Re­search and Therapy, and Dr. Ravi Vij from Washington Uni­ver­sity School of Medicine.

The Bottom Line: Incremental Steps In The Right Direction, But Nothing Game Changing

Overall, there was some good news for myeloma patients and care­givers that came out of this year’s ASCO meeting.

But as is typ­i­cally the case, there was not as much re­search pre­sented at ASCO as there was at the past American Society of He­ma­tol­ogy (ASH) meeting, and none of the ASCO re­search can be con­sidered earth-shattering.

Nonetheless, there were some highlights to the ASCO meeting.

There was en­cour­ag­ing re­search on the poten­tial myeloma treat­ment quisinostat, which has not re­ceived much attention in the past, and which works dif­fer­en­tly than existing myeloma ther­a­pies such as Revlimid (lena­lido­mide) and Velcade (bor­tez­o­mib).

There also were up­dates about poten­tial treat­ments that have been discussed at pre­vi­ous meetings, and which con­tinue to show prom­ise.  Treatments in this category in­clude daratumumab, elotuzumab, and ixazomib (MLN9708).

In addi­tion, there con­tinued to be good news about Kyprolis (car­filz­o­mib) and Pomalyst (poma­lido­mide), which were recently approved as new myeloma ther­a­pies by the U.S. Food and Drug Admin­istra­tion (FDA).  In par­tic­u­lar, the re­­sults of one of the Pomalyst stud­ies will likely lead to ap­prov­al of the drug in Europe.

These devel­op­ments mean that the list of treat­ment op­tions avail­able to myeloma patients and spe­cialists can be ex­pec­ted to grow in the com­ing years.  More treat­ment op­tions, in turn, are likely to re­­sult in fur­ther im­prove­ments in the sur­vival of myeloma patients.  And that is definitely good news.

Yet, from the perspective of a myeloma patient, it seems dif­fi­cult to argue that the re­­sults pre­sented at the ASCO meeting rise to a level beyond “good.”

As promising as the many new myeloma treat­ments are, there was no convincing evi­dence that any of them will be real game changers.

Dr. Vij seemed to agree when he said “There was nothing very path-breaking on myeloma at ASCO.”

Furthermore, most of the new treat­ments pre­sented at ASCO are a num­ber of years away from being readily avail­able to most myeloma patients. Elotuzumab is likely to be the first of these drugs to be approved for myeloma, and its ap­prov­al is not ex­pec­ted until later next year, at the earliest.

In addi­tion, a num­ber of key controversies re­lated to the treat­ment of mul­ti­ple myeloma still remain un­an­swered: How many treat­ments and which treat­ments should be used for newly diag­nosed patients?  Should all trans­plant-eligible patients undergo stem cell trans­plan­ta­tion at some point during the course of their dis­ease, and if so, what is the optimal timing of trans­plan­ta­tion?  Is main­te­nance ther­apy beneficial, and if so, how long should it be admin­istered?

The myeloma spe­cialists The Beacon consulted identified a few stud­ies that attempted to shed some light on these questions.  One study, for example, com­pared stem cell trans­plan­ta­tion with novel agent ther­apy and also in­ves­ti­gated the ben­e­fits of main­te­nance ther­apy.  Another study eval­u­ated a new technique for detecting minimal residual dis­ease, which could help physicians de­ter­mine which patients should re­ceive fur­ther treat­ment.  Neither of these stud­ies, though, settled any of the key controversies.

New Agents Being Tested For Myeloma

Highlights from the ASCO meeting cer­tainly in­cluded re­search re­­sults for a num­ber of new myeloma ther­a­pies.

Results pre­sented at the meeting ranged from promising initial clin­i­cal trial re­­sults for one new drug, qui­sin­ostat, to up­dated re­­sults from early-stage clin­i­cal trials for a couple of drugs, to up­dated re­­sults from a late-stage clin­i­cal trial for elotuzumab.

Quisinostat

Although clin­i­cal trial re­­sults were pre­sented at ASCO for a num­ber of new treat­ments being in­ves­ti­gated for myeloma, quisinostat was the only one that made its first appearance at ASCO (poster [PDF] courtesy of Dr. Xavier Leleu).

Referring to a study about quisinostat and another study of the re­lated drug panobinostat, Dr. van Rhee said, “The histone deacetylase in­hib­i­tors panobinostat and quisinostat when com­bined with Velcade and dexa­metha­sone [Decadron] were reported to induce re­sponses in re­lapsed and re­frac­tory, in­clud­ing Velcade-refractory, myeloma patients.”

Daratumumab

Although the rest of the new myeloma treat­ments in this article are ones that have been discussed at sev­er­al pre­vi­ous med­i­cal meetings, the up­dated re­­sults pre­sented at this year’s ASCO meeting demon­strate that these drugs con­tinue to show prom­ise as myeloma treat­ments.

Among the new drugs the myeloma spe­cialists mentioned as par­tic­u­larly promising, an anti­body known as daratumumab was the only one mentioned by almost all of the myeloma spe­cialists The Beacon consulted about the ASCO meeting (presentation [pdf] courtesy of Dr. Lokhorst).

Dr. van Rhee ex­plained that although dara­tu­mu­mab is earlier in devel­op­ment than elotuzumab, “Dara­tu­mu­mab is of interest since it exhibited single-agent ac­­tiv­ity in re­lapsed and re­frac­tory patients during a dose-escalation study and induced partial re­sponses.”

“Daratumumab's data con­tinues to look ex­cit­ing re­gard­ing re­sponse rates,” said Dr. Vij.

Dr. Kumar also stated that it is “very in­ter­est­ing data, and dara­tu­mu­mab clearly appears to be a promising drug.” He pointed out, how­ever, that “concerns remain about in­fusion reac­tions and isolating the effect of the anti­body from the steroids” which patients also have re­ceived during treat­ment with dara­tu­mu­mab.

Elotuzumab

Elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone con­tinued to demon­strate high re­sponse rates and fa­vor­able pro­gres­sion-free sur­vival in re­lapsed and re­frac­tory patients (poster [PDF] courtesy of Dr. Sagar Lonial).

“Elotuzumab showed good ac­­tiv­ity in the re­lapsed / re­frac­tory setting in com­bi­na­tion with dexa­meth­a­sone and Revlimid,” said Dr. van Rhee. “Phase 3 stud­ies are presently recruiting,” he added.

Dr. Vij in­di­cated that the re­­sults of this Phase 3 study could be prac­tice changing.

Ixazomib

Ixazomib (MLN9708) as a single-agent ther­apy also con­tinued to dem­onstrate re­sponses in re­lapsed and re­frac­tory myeloma patients (presentation [pdf] courtesy of Dr. Kumar).

“In a Phase 1 study, the oral pro­te­a­some in­hib­i­tor ix­az­o­mib was well tol­er­ated and showed ac­­tiv­ity in a heavily pre-treated patient pop­u­la­tion without causing severe neu­rop­athy,” ex­plained Dr. van Rhee. Neu­rop­athy is nerve damage that can cause pain, tingling, and numbness in the hands and feet.

“Weekly ix­az­o­mib data shows the drug has single-agent ac­­tiv­ity in re­lapsed and re­frac­tory dis­ease,” said Dr. Vij. He, as well, noted that the drug has low rates of periph­eral neu­rop­athy.

Dr. Kumar also remarked that ix­az­o­mib has “promising single-agent ac­­tiv­ity, and neurotoxicity appears lim­ited.” He pointed out, though, that the data “needs val­i­da­tion from larger patient groups treated for longer periods.”

Pomalyst And Kyprolis

A num­ber of stud­ies involving Pomalyst (poma­lido­mide) and Kyprolis (car­filz­o­mib) were discussed at this year’s ASCO meeting. The FDA approved both of these drugs within the last year for the treat­ment of re­lapsed and re­frac­tory myeloma.

The latest data on these two drugs con­tinue to sup­port their ef­fec­tiveness.  One study, how­ever, in­di­cates Kyprolis should be used with caution in patients with existing serious heart dis­ease.

“Several stud­ies [presented at ASCO] sup­port the notion that the recently approved drugs Pomalyst and Kyprolis are con­tri­bu­tions to the armamentarium for re­lapsed / re­frac­tory myeloma in­clud­ing patients with mod­er­ate [kidney] im­pair­ment and adverse cytogenetics [chromosomal ab­nor­mal­i­ties],” said Dr. van Rhee.

Pomalyst

The ef­fi­cacy and safety of Pomalyst plus low-dose dexa­meth­a­sone were discussed during a num­ber of ASCO pre­sen­ta­tions.  The com­bi­na­tion ther­apy was com­pared to treat­ment with high-dose dexa­meth­a­sone alone, and it also was eval­u­ated in spe­cif­ic subsets of re­lapsed and re­frac­tory myeloma patients such as older patients, those with kidney im­pair­ment, and those with chromosomal ab­nor­mal­i­ties.

“A ran­domized Phase 3 study showed im­proved over­all sur­vival for patients treated with Pomalyst and low-dose dexa­meth­a­sone who had failed both Revlimid and Velcade,” said Dr. van Rhee.  The im­proved sur­vival was in comparison to treat­ment with high-dose dexa­meth­a­sone alone (presentation [pdf] courtesy of Dr. Katja Weisel).

These re­­sults are good news for Euro­pean myeloma patients.  Dr. Vij stated that these re­­sults “will lead to ap­prov­al of the drug [Pomalyst] in Europe.”

Dr. Krishnan also cited the importance of a Phase 1 study that in­di­cates Pomalyst plus Velcade and low-dose dexa­meth­a­sone is ef­fec­tive for re­lapsed and re­frac­tory myeloma patients (poster [PDF] courtesy of Dr. Paul Richardson).

Kyprolis

Dr. van Rhee said, “Kyprolis con­tinues to show promising re­­sults both in newly diag­nosed patients and in the re­lapsed / re­frac­tory setting, in­clud­ing patients who failed Revlimid or Velcade.”

The only spe­cif­ic Kyprolis study that any of the myeloma experts mentioned, though, is a retro­spec­tive­ analy­sis that showed nearly a fifth of heavily pre­treated myeloma patients who re­ceived treat­ment with Kyprolis ex­peri­enced heart-related com­pli­ca­tions.  Most of these patients had preexisting risk factors for heart-related com­pli­ca­tions.  The re­searchers there­fore sug­gest using Kyprolis with caution in patients with a history of serious cardiac dis­ease (poster [pdf] courtesy of Dr. Saad Usmani).

“As we are using the drug in more patients and earlier in the dis­ease course, this in­­for­ma­tion is im­por­tant in patient selection for the drug as well as in monitoring for side effects,” said Dr. Krishnan.

Stem Cell Transplantation And Maintenance Therapy

Another study was mentioned by almost all of the myeloma spe­cialists The Beacon consulted about the ASCO meeting.  It is one that eval­u­ated the importance of stem cell trans­plan­ta­tion as well as main­te­nance ther­apy (presentation [pdf] courtesy of Dr. Palumbo).

All patients in the study re­ceived initial ther­apy with four cycles of Revlimid and dexa­meth­a­sone. After that, half the patients were ran­domly selected to re­ceive con­sol­i­da­tion ther­apy with melphalan (Alkeran), pred­ni­sone, and Revlimid (MPR), while the other half re­ceived con­sol­i­da­tion with high-dose mel­phalan followed by an au­tol­o­gous (own) stem cell trans­plant.

After their con­sol­i­da­tion ther­a­pies, the patients were once again ran­domized to re­ceive either no main­te­nance ther­apy or main­te­nance ther­apy with Revlimid.

Dr. Vij summarized the re­­sults by saying, “Transplantation is superior to MPR ac­cord­ing to pro­gres­sion-free sur­vival, and main­te­nance ther­apy is superior in terms of both pro­gres­sion-free sur­vival and over­all sur­viv­al.”  He pointed out, how­ever, that the design of the study makes interpretation of the main­te­nance data dif­fi­cult.

Dr. Kumar agreed that the study “highlights the value of trans­plan­ta­tion as a con­sol­i­da­tion [therapy].”  He did not feel, how­ever, that six cycles of MPR ther­apy was really suf­fi­cient ther­apy, going so far as to say that the the patients who re­ceived that ther­apy, com­bined with no main­te­nance ther­apy, re­ceived "very inadequate ther­apy."

He there­fore cautions that no conclusions should be drawn from the study except that “transplantation is still an ef­fec­tive con­sol­i­da­tion, and short duration of Revlimid-dexamethasone ther­apy plus MPR is not to be used.”

Minimal Residual Disease

Almost all of the myeloma spe­cialists also highlighted a study reporting on the use of a new method, known as deep sequencing, to detect minimal residual dis­ease (MRD) in myeloma patients (abstract).  The tech­nique may be able to detect more cases of residual myeloma than the most common cur­rent method of determining MRD status, multiparameter flow cytometry.

Similar to pre­vi­ous stud­ies, the re­­sults of the deep-sequencing study show that patients with no residual dis­ease after treat­ment have better over­all sur­vival than those who still have residual dis­ease.

Dr. Krishnan said that the re­­sults are “very in­ter­est­ing in fur­ther proof of principle that ther­apy to get to an MRD-negative state may be our new goal. Though, it still begs the question how best to achieve that re­­sult, e.g., induction plus trans­plan­ta­tion and con­sol­i­da­tion, multidrug induction alone, etc.”

Dr. van Rhee added that “Prospective stud­ies will have to address the question whether MRD can be used both to guide the type of ther­apy admin­istered and the duration of treat­ment.”

Although the deep-sequencing study was broadly seen by the myeloma spe­cialists The Beacon surveyed as one of the highlights of the ASCO meeting, not all of them feel deep sequencing is a sig­nif­i­cant im­prove­ment.

Dr. Kumar described deep sequencing as “promising tech­nology,” but pointed out that it is still lim­ited by the need for base­line samples.  Dr. Vij went a step fur­ther, saying that he did not feel the deep-sequencing study dem­onstrated that the new tech­nology is  superior to multiparameter flow cytometry.

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All of The Beacon’s coverage re­lated to the ASCO 2013 meeting can be found here.

Note: Electronic copies of conference pre­sen­ta­tions and posters made avail­able to the Beacon's readers are for personal use only. Fur­ther transmission or pub­li­ca­tion of the files is not permitted, although hyperlinks to the files are permitted with attribution to the author and to The Beacon (for example, "courtesy of Dr. Jane Doe and The Myeloma Beacon.")