This year’s American Society of Clinical Oncology (ASCO), which was held in Chicago, began on Friday and concluded on Tuesday.

Monday was the busiest day at the meeting with regard to myeloma re­search.  It featured a session of oral pre­sen­ta­tions in the morn­ing and a poster session in the afternoon.

This up­date summarizes the myeloma-related stud­ies pre­sented during the afternoon poster session, which was the final myeloma-related session of the meeting. An earlier article covered the findings from the oral pre­sen­ta­tions that were given in the morn­ing.

Most of the key posters at Monday's poster session focused on re­­sults from clin­i­cal trials of po­ten­tial new myeloma treat­ments.

There also was a poster, how­ever, that shed light on an im­por­tant topic in the treat­ment of mul­ti­ple myeloma: the optimal timing of stem cell trans­plan­ta­tion.

The content in the Beacon's daily up­dates is based on the actual pre­sen­ta­tions and posters pre­sented at the meeting, which often differ in terms of their content com­pared to what is avail­able prior to the meeting in abstracts sub­mitted for the meeting.

The Beacon’s ASCO up­dates also in­clude links to pre­sen­ta­tions and posters that the ASCO presenters have made avail­able to the Beacon’s readers for review. The Beacon’s meeting-related articles will be up­dated reg­u­larly as more presenters make their slide decks and posters avail­able to The Beacon. The “updated” time at the top of up­dated articles allows readers to see if new files or other content have been added.

Quisinostat

One poster summarized re­­sults from a Phase 1b study of the inves­ti­ga­tional drug quisinostat (JNJ-26481585) in com­bi­na­tion with Velcade (bor­tez­o­mib) and dexa­­metha­­sone (Decadron) (abstract; poster [PDF] courtesy of Dr. Xavier Leleu).

Quisinostat, which is being devel­oped by Johnson & Johnson (NYSE: JNJ), is an oral histone deacetylase (HDAC) in­hib­i­tor.  Other HDAC in­hib­i­tors in­clude Zolinza (vorinostat) and panobinostat.  The drugs in this class work by interrupting cell division and causing cell death.

The quisinostat study in­cluded 18 patients with a median age of 69 years who had re­ceived a median of two prior ther­a­pies. Half of the patients had pre­vi­ously re­ceived Velcade.

Patients were treated with one of four doses of quisinostat along with Velcade and dexa­meth­a­sone. The max­i­mum tol­er­ated dose of quisinostat was found to be 10 mg.

The over­all re­sponse rate for the patients was 88 per­cent, with 6 per­cent achiev­ing a com­plete re­sponse, 18 per­cent a very good partial re­sponse, and 64 per­cent a partial re­sponse.

The pro­gres­sion-free sur­vival and over­all sur­vival re­­sults are not yet avail­able.

The most common side effects of any degree of severity observed during the study in­cluded fatigue (56 per­cent), low platelet counts (50 per­cent), diarrhea (44 per­cent), and swelling (22 per­cent). Doses of 10 mg or higher of quisinostat were asso­ci­ated with heart-related side effects.

Elotuzumab

Updated re­­sults from a Phase 1/2 study of elotuzumab in com­bi­na­tion with Revlimid (lena­lido­mide) and dexa­meth­a­sone also were pre­sented during the poster session (abstract; poster [PDF] courtesy of Dr. Sagar Lonial).

Elotuzumab, like daratumumab and siltuximab, belongs to a class of drugs known as mono­clonal anti­bodies. It works by identifying pro­teins on the surface of myeloma cells and signaling the im­mune sys­tem to destroy those cells.

Preliminary re­­sults from the study showed that elotuzumab has promising ac­­tiv­ity in myeloma (see re­lated Beacon news). Specifically, the over­all re­sponse rate to the elotuzumab-Revlimid-dexamethasone com­bi­na­tion was 84 per­cent. The re­sponse rate was higher in patients who re­ceived a 10 mg/kg dosing of elo­tu­zu­mab (92 per­cent), com­pared to 76 per­cent observed in the patients who re­ceived a 20 mg/kg dosing.

Updated sur­vival re­­sults were summarized in Monday's poster.

After a median follow-up of 20.8 months, the median pro­gres­sion-free sur­vival was 33 months for patients who re­ceived 10 mg/kg and 18.6 months for those who re­ceived 20 mg/kg.  The median over­all sur­vival was not reported.

The most common severe side effects were low lym­pho­cyte levels (19 per­cent), low neu­tro­phil counts (18 per­cent), low platelet counts (16 per­cent), and low red blood cell counts (14 per­cent). The re­searchers did not observe any new side effects since pre­vi­ously reporting on the drug's safety;  most treat­ment-related side effects oc­curred within the first 18 months of treat­ment.

Across all patients in the study, 15 per­cent dis­con­tinued treat­ment due to side effects.  This rate was lower (8 per­cent), how­ever, in the patients who re­ceived the 10 mg/kg dose of elotuzumab.

Kyprolis

Another poster during the session summarized the final re­­sults of a Phase 1/2 study of Kyprolis (car­filz­o­mib) plus Revlimid and low-dose dexa­meth­a­sone, commonly abbre­vi­ated as CRd, in patients with re­lapsed and re­frac­tory mul­ti­ple myeloma (abstract; poster [PDF] courtesy of Dr. Michael Wang).

Previously reported re­­sults from the study showed that the com­bi­na­tion is ef­fec­tive in the study patient pop­u­la­tion (see re­lated Beacon news).

The study in­cluded 84 patients with a median age of 62 years and who had re­ceived a median of two prior ther­a­pies. Approximately three quarters (77 per­cent) had pre­vi­ously re­ceived Velcade, and 70 per­cent had pre­vi­ously re­ceived Revlimid.

At a median follow-up time of 24.4 months, the over­all re­sponse rate was 69 per­cent, with 5 per­cent achiev­ing a com­plete re­sponse, 36 per­cent a very good partial re­sponse, and 29 per­cent a partial re­sponse. Median duration of re­sponse was 18.8 months.

The median pro­gres­sion-free sur­vival was 11.8 months. The median over­all sur­vival was not reported.

The most common side effects of any grade in­cluded fatigue (66 per­cent), diarrhea (56 per­cent), and low white blood cell counts (45 per­cent). Severe periph­eral neu­rop­athy (pain, tingling, and loss of sensation in the extremities) was observed in only 1 per­cent of patients.

Overall, 21 per­cent of patients in the study dis­con­tinued treat­ment due to side effects.

Panobinostat

Another poster summarized findings of a sub-analysis of a Phase 2 study of panobinostat plus Velcade and dexa­meth­a­sone in re­lapsed patients who were re­frac­tory to Velcade (abstract).

Panobinostat is being devel­oped by the pharma­ceu­tical com­pany Novartis (NYSE: NVS) for a variety of dif­fer­ent cancers.  As mentioned earlier, it belongs to the class of drugs known as histone deacetylase (HDAC) in­hib­i­tors.

Previously reported re­­sults of the Phase 2 study showed that the panobinostat com­bi­na­tion may be ef­fec­tive in re­lapsed patients who were re­frac­tory to Velcade (see re­lated Beacon news).

Specifically, the over­all re­sponse rate was 35 per­cent and the median pro­gres­sion-free sur­vival time was 5.4 months.

The cur­rent poster in­cluded fur­ther re­­sults on re­sponse rates and pro­gres­sion-free sur­vival based on patient char­ac­ter­istics at the beginning of the study.

Approximately half of the patients (49 per­cent) had re­ceived Velcade in their last prior line of ther­apy; among those, 73 per­cent progressed while on Velcade and 27 per­cent progressed within 60 days of com­plet­ing their Velcade regi­men.

The re­­sults showed that patients who did not re­ceive Velcade as part of their last prior ther­apy had a sig­nifi­cantly higher over­all re­sponse rate (43 per­cent) than patients who had Velcade as part of their most recent ther­apy (26 per­cent).

Progression-free sur­vival was also higher in patients who did not re­ceive Velcade as part of their last ther­apy (6 months) com­pared to those who did (4.9 months).

Patients who progressed while on Velcade had a higher over­all re­sponse rate (38 per­cent) than patients who progressed within 60 days of Velcade ther­apy (27 per­cent).

Progression-free sur­vival, on the other hand, was longer for patients who progressed within 60 days of Velcade (7.6 months), com­pared to patients who progressed while on Velcade (4.2 months).

Autologous Stem Cell Transplantation After RVD Treatment

The session also in­cluded a poster re­lated to the timing of au­tol­o­gous (own) stem cell trans­plan­ta­tion in newly diag­nosed myeloma patients who have re­ceived initial treat­ment with Revlimid, Velcade, and dexa­metha­sone, commonly referred to as RVD (abstract; poster [PDF] courtesy of Dr. Ajay Nooka).

The analysis was based on a retro­spec­tive review of data from 222 newly diag­nosed myeloma patients treated at Emory Uni­ver­sity's Winship Cancer In­sti­tute.  All patients re­ceived at least two cycles of RVD as their initial myeloma treat­ment, and all patients were eli­gible at diag­nosis to undergo au­tol­o­gous stem cell trans­planta­tion.

Overall, 62 per­cent of patients underwent stem cell trans­plan­ta­tion soon after com­plet­ing their initial RVD ther­apy.

The remaining 38 per­cent of patients delayed trans­plan­ta­tion due to risk, re­sponse, side effects of RVD, or patient pref­er­ence.  Among those, 66 per­cent underwent delayed trans­plan­ta­tion during the course of the study and 33 per­cent had not yet undergone trans­plan­ta­tion.

Eighty per­cent of the patients who delayed their stem cell trans­plant re­ceived a Revlimid-based main­te­nance ther­apy after their initial RVD ther­apy was com­plete.  About 60 per­cent of the patients in the early-transplant group re­ceived main­te­nance ther­apy after their trans­plant.

The re­searchers found that after a median follow-up of 31 months, the pro­gres­sion-free sur­vival times for the early and delayed trans­plant groups were 45 months and 47 months, re­spec­tively.

The median over­all sur­vival times were not yet reached for both treat­ment groups. However, the delayed trans­plan­ta­tion group has noticeably better over­all sur­vival at this point, with a 50-month over­all sur­vival rate of about 90 per­cent, com­pared to 80 per­cent for the early trans­plan­ta­tion patients.

In an analysis of the study re­­sults by patient char­ac­ter­istics, the re­searchers found that sur­vival dif­fer­ences be­tween the early and late trans­plant patients were the most pronounced among male patients, patients under the age of 65 years, and patients without high-risk chromosomal ab­nor­mal­i­ties.

They re­searchers state that, although their re­­sults may be affected by selection bias, they in­di­cate that delayed stem cell trans­plan­ta­tion is a feasible op­tion in select newly diag­nosed myeloma patients.

───────────────── ♦ ─────────────────

Additional coverage of key re­search re­­sults from the ASCO 2013 meeting will con­tinue in com­ing days with in­di­vid­ual, topic-specific news articles.  For all Beacon articles re­lated to this year’s ASCO meeting, see The Beacon’s full ASCO 2013 coverage.

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.")