It has been ten days since the 2011 annual meeting of the American Society of He­ma­tol­ogy (ASH) came to a close.

Since the meeting started, The Beacon has been providing detailed coverage in the form of discussion forum postings, daily up­dates, and in-depth articles about key re­search findings.

In this and The Beacon's next article about the meeting, how­ever, the per­spective changes a bit.

The focus shifts to the bigger picture -- to questions like: "What was the im­pact of the meeting?", and "What are the meeting's implications for the treat­ment of myeloma patients in the near future?"

There was so much re­search pre­sented at the meeting that it is still a chal­lenge to answer such questions definitively.

For some initial thoughts about "the big picture," how­ever, The Beacon turned to its Medical Advisors -- the tal­ented myeloma spe­cialists who share their knowledge and ex­per­tise in the Beacon's dis­cus­sion forum.

The Medical Advisors were asked for their initial thoughts on what the top re­search findings of the meeting were, and also what they con­sidered to be the "hidden gems" of the meeting.

This article passes along the re­sponses The Beacon re­ceived re­gard­ing the top re­search findings.  A future article will review the re­sponses re­gard­ing "hidden gems."

Dr. Peter Voorhees from the Uni­ver­sity of North Carolina at Chapel Hill:

The up­dated data pre­sented on the use of the next gen­er­a­tion immuno­modu­la­tory agent, pomalidomide, and the next gen­er­a­tion pro­te­a­some in­hib­i­tor, carfilzomib, remained promising.

Newly pre­sented data on Millennium's novel oral pro­te­a­some in­hib­i­tor, MLN9708 (ixazomib), grabbed a lot of attention (see re­lated Beacon news).  The data in heavily pre­treated patients was respectable, and the re­­sults of MLN9708 in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron) in newly-diagnosed myeloma patients were impressive, with a re­sponse rate of 100 per­cent (although the num­ber of patients treated with this regi­men thus far is small).

Notably, periph­eral neu­rop­athy was not as common and was of lesser severity when com­pared with historical re­­sults for Velcade (bor­tez­o­mib).

If these re­­sults hold up, MLN9708 may provide a way to treat patients with user-friendly, all-oral pro­te­a­some in­hib­i­tor and immuno­modu­la­tory agent com­bi­na­tions.

It remains dif­fi­cult to de­ter­mine what new class of drugs will next break out onto the myeloma scene.

Results from the Phase 3 study of the histone deacetylase in­hib­i­tor, Zolinza (vorinostat), in com­bi­na­tion with Velcade, were pre­sented.  Although the re­sponse rate with Velcade and Zolinza was clearly higher than with Velcade alone, there was no clin­i­cally sig­nif­i­cant dif­fer­ence in pro­gres­sion-free sur­vival.

Nonetheless, the re­sponse rate was higher with the com­bi­na­tion and the data from the Phase 2 study of Velcade and Zolinza in patients with re­lapsed and re­frac­tory myeloma were en­cour­ag­ing.  As such, fur­ther in­ves­ti­ga­tion of this class of agents is warranted.

Updated re­­sults from the Phase 2 study of the anti-CS1 mono­clonal anti­body, elotuzumab, in com­bi­na­tion with Revlimid and dexa­meth­a­sone were quite impressive, producing re­sponse rates that were higher than what would be ex­pected for Revlimid and dexa­meth­a­sone alone (see re­lated Beacon news).

Ongoing Phase 3 trials in re­lapsed patients and newly-diagnosed, trans­plant-ineligible patients com­par­ing Revlimid and dexa­meth­a­sone with or without elotuzumab will help de­ter­mine the role of this drug in myeloma ther­apy.

Dr. Ken Shain from the Moffitt Cancer Center in Tampa:

I con­tinue to be impressed by the ac­­tiv­ity of the CS-1 anti­body elotuzumab pre­sented by Dr. Sagar Lonial from the Winship Cancer In­sti­tute in Atlanta in an oral session Monday morn­ing.

This mono­clonal anti­body con­tinues to dem­onstrate ex­cel­lent com­bi­na­tion ac­­tiv­ity with Revlimid and low-dose dexa­meth­a­sone in the re­lapsed setting.

Overall re­sponse rates were as high as 92 per­cent in the 10 mg/kg dosing group; very good partial re­sponse rates were in the 40 plus per­cent range. And, im­por­tantly, the regi­men was well tol­er­ated with appro­pri­ate premedication ther­apy.

Therefore, Dr. Lonial and colleagues have identified a novel com­bi­na­tion ther­apy that may have a sig­nif­i­cant im­pact on how we treat myeloma in the very near future.

I always feel that the re­lapsed and re­frac­tory pop­u­la­tions are the patients that need the most assistance in a dis­ease where cure is not yet an end­point.

To this end, the better tol­er­ated and more active com­­pounds and com­bi­na­tion ther­a­pies we have avail­able to us, the better.

Dr. Adam Cohen from the Fox Chase Cancer Center in Philadelphia:

There were no truly prac­tice-changing data pre­sented for myeloma at ASH this year.

However, a few noteworthy stud­ies with emerging agents stood out -- two stud­ies with en­cour­ag­ing re­­sults, and one with disappointing out­comes.

Dr. Andrzej Jakubowiak of the Uni­ver­sity of Chicago pre­sented up­dated data on the use of car­filz­o­mib in com­bi­na­tion with Revlimid and dexa­meth­a­sone for newly-diagnosed myeloma.

Of 53 patients, 94 per­cent responded, with 53 per­cent achieving near com­plete or com­plete remission, and after a median of eight cycles of ther­apy, there were no cases of severe periph­eral neu­rop­athy, which is a big change from Velcade-based induction regi­mens.

Median follow-up is only 9.5 months, so we need to wait and see how durable these re­sponses will be.

Dr. Paul Richardson from the Dana-Farber Cancer In­sti­tute pre­sented re­­sults from a ran­domized Phase 2 study of poma­lido­mide plus dexa­meth­a­sone versus poma­lido­mide alone in 221 heavily pre­treated re­lapsed/refractory patients.

The over­all re­sponse rate was 34 per­cent for poma­lido­mide plus dexa­meth­a­sone, versus 13 per­cent for poma­lido­mide alone.

Importantly, the over­all re­sponse rate was 30 per­cent in patients re­frac­tory to Velcade and Revlimid -- a group with few cur­rently avail­able op­tions.

Finally, Dr. Meletios Dimopoulos from the Uni­ver­sity of Athens in Greece reported the first re­­sults from the VANTAGE 088 trial, the first ran­domized Phase 3 study com­par­ing the HDAC in­hib­i­tor Zolinza plus Velcade to Velcade alone in re­lapsed myeloma patients.

The re­sponse rate was higher in the com­bi­na­tion arm (56 per­cent versus 41 per­cent), and the trial did meet its pri­mary end­point, which was to im­prove pro­gres­sion-free sur­vival.

However, this im­prove­ment was only 0.8 months (7.6 months for Zolinza plus Velcade versus 6.8 months for Velcade alone). There was no sig­nif­i­cant dif­fer­ence in over­all sur­vival, and toxicity was sig­nif­i­cantly greater in the com­bi­na­tion arm.

So this was hardly a home run -- maybe a bunt single? -- and not likely to change prac­tice.

Note: The Advisor re­sponses summarized above have been edited slightly for length, flow, and adherence to Beacon conventions (regarding, for example, drug names).