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ASCO 2013 Multiple Myeloma Update – Day Four: Poster Presentations

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Published: Jun 6, 2013 11:06 am

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 (abstractposter [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.

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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.”)

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