This year’s American Society of Hematology (ASH) meeting con­tinues in Atlanta.  Yesterday was the third day of the meeting and the busiest day in terms of myeloma-related presentations.  It was packed full of both oral and poster presentations.

There were so many myeloma-related talks given yesterday that many of them were held simultaneously.  The Beacon will therefore summarize presentations from the four most important sessions in updates such as this one.

This update covers presentations from the second of the four key oral presentation sessions.  An update published yesterday covers presentations from the first session (see related Beacon news), and updates to be published later today and tomorrow will cover the remaining two key oral presentation sessions as well as a poster session held yesterday evening.

The late morning oral presentation session to be discussed in this update focused on treat­ment options for multiple myeloma patients.  Each of the talks during the session presented results from clinical trials investigating either potential new myeloma treat­ments or the recently-approved Kyprolis (car­filz­o­mib), often in com­bi­na­tion with current myeloma treat­ments.

Two of the presentations were about pomalidomide studies, including the final data from the Phase 2 study that is the basis for the poma­lido­mide application to the U.S. Food and Drug Administration.

The results of the ARRY-520 (filanesib) study presented during this session seem particularly promising, given how heavily pretreated the study population was.  Furthermore, for both ARRY-520 and another potential new drug discussed during the session (tabalumab), the study investigators found a marker than can be used to predict which patients are more likely to respond to the drugs.

Kyprolis, Thalidomide, Cyclophosphamide, And Dexamethasone

The first presentation of the session was given by Dr. Joseph Mikhael from the Mayo Clinic in Scottsdale, Arizona.  Dr. Mikhael presented results from a Phase 2 study of a com­bi­na­tion of Kyprolis, thalidomide (Thalomid), cyclophosphamide (Cytoxan), and dexamethasone (Decadron), which is often referred to as “CYCLONE” (abstract; presentation slide deck (pdf) made available by Dr. Mikhael as a courtesy to the Beacon’s readers).

Results from the first 27 patients enrolled in the study were pre­vi­ously reported.  After addi­tional studies indicated that higher doses of Kyprolis may be safe and more effective, more patients were enrolled in the current study to test higher doses of Kyprolis in the CYCLONE com­bi­na­tion.

In total, 38 newly diagnosed myeloma patients eligible for stem cell trans­plan­ta­tion were enrolled in the study.  Their median age was 62 years.

Among the 27 initial patients in the study, the over­all response rate was 96 per­cent.  Specifically, 26 per­cent achieved a complete response, 48 per­cent a very good partial response, and 22 per­cent a partial response.

The most common severe side effects were low white blood cell counts (16 per­cent neu­tro­penia and 8 per­cent lymphopenia), irregular heart beat (11 per­cent), increased liver function tests (6 per­cent), fatigue (6 per­cent), muscle weakness (6 per­cent), and blood clots (6 per­cent).  Two patients developed pneu­monia that required hospi­tal­iza­tion.  Additionally, 24 per­cent developed mild periph­eral neu­rop­athy (pain, tingling, or loss of sensation in the extremities, and a common side effect of thalido­mide).

Pomalidomide, Cyclophosphamide, And Prednisone

The second talk was given by Dr. Antonio Palumbo from the University of  Torino in Italy.  He presented results from a Phase 1/2 study of poma­lido­mide in com­bi­na­tion with cyclophosphamide and prednisone in myeloma patients pre­vi­ously treated with Revlimid (lena­lido­mide) (abstract; presentation slide deck (pdf) made available by Dr. Palumbo as a courtesy to the Beacon's readers).

After six cycles of initial treat­ment with poma­lido­mide, cyclophosphamide, and pred­ni­sone, patients received main­te­nance ther­apy with poma­lido­mide and pred­ni­sone.

Pomalidomide is an immuno­modu­la­tory agent, meaning that it works by inducing a patient’s immune system to attack and destroy myeloma cells. It belongs to the same class of drugs as thalidomide and Revlimid.

Pomalidomide is being developed by Celgene Corporation (NASDAQ: CELG), the same com­pany that markets Revlimid and thalido­mide in the United States and inter­na­tionally.

The study included 69 people who had been diagnosed with myeloma a median of 4.6 years before.  The median age was 69 years, and the participants had received a median of 3 prior ther­a­pies.

Among the 55 participants who were evaluated for response, the over­all response rate after initial ther­apy with poma­lido­mide, cyclophosphamide, and dexa­meth­a­sone was 51 per­cent, with 6 per­cent achieving a complete response, 18 per­cent a very good partial response, and 27 per­cent a partial response.

Further analysis showed that over­all response rates were 46 per­cent for patients refractory (did not respond) to Revlimid, 61 per­cent for patients who re­lapsed after Revlimid ther­apy, and 50 per­cent for patients refractory to both Revlimid and Velcade.

After main­te­nance ther­apy, the over­all response rate was 53 per­cent, with 6 per­cent achieving a complete response, 23 per­cent a very good partial response, and 24 per­cent a partial response.

At a median follow-up of 14.8 months, the median pro­gres­sion-free survival time was 10.4 months and the one-year over­all survival rate was 69 per­cent.

Severe side effects included rash (7 per­cent), in­fec­tions (5 per­cent), and neurologic (5 per­cent).  Life-threatening side effects included low white blood cell counts (16 per­cent) and low platelets (5 per­cent).  Additionally, 2 per­cent of patients developed blood clots and 4 per­cent died due to in­fec­tions.

Tabalumab Plus Velcade

The next presentation was given by Dr. Noopur Raje from the Massachusetts General Hospital in Boston, who discussed results from a Phase 1 study of tabalumab in com­bi­na­tion with Velcade (bor­tez­o­mib) and, in some cases, dexa­meth­a­sone (abstract).

Tabalumab (also known as LY2127399) is being developed by Eli Lilly (NYSE: LLY).  It is an anti­body that targets a protein called BAFF, which plays an important role in the devel­op­ment of B cells.  Excessive levels of BAFF lead to ab­nor­mally high levels of anti­body pro­duc­tion.  Therefore, tabalumab may be effective for multiple myeloma as well as autoimmune diseases.  Preclinical studies have indicated that tabalumab is effective against myeloma and also helps prevent bone destruction.

The study included 48 multiple myeloma patients with a median age of 66 years and who had been treated with a median of three prior ther­a­pies.  Three-quarters of the participants were treated with tabalumab plus Velcade; the remaining quarter also received dexa­meth­a­sone.

In total, 46 per­cent of patients responded to the ther­apy, with 4 per­cent achieving a complete response, 8 per­cent a very good partial response, and 33 per­cent a partial response.

The researchers found that patients who responded to the tabalumab com­bi­na­tion ther­apy were more likely to have low levels of BAFF in their blood prior to treat­ment.

Among 14 patients assessed, the median time to pro­gres­sion was 4.9 months.

The most common severe side effects were low platelet counts (23 per­cent), pneu­monia (13 per­cent), periph­eral neu­rop­athy (13 per­cent), low white blood cell counts (10 per­cent), kidney failure (8 per­cent), diarrhea (6 per­cent), low red blood cell counts (6 per­cent), and mus­cu­lo­skel­etal pain (6 per­cent).  One patient died due to acute res­pira­tory distress syn­drome.

A Phase 2/3 study of the same drug com­bi­na­tion is cur­rently recruiting participants.  Tabalumab will be tested at two different doses in com­bi­na­tion with Velcade and dexa­meth­a­sone as compared to Velcade plus dexa­meth­a­sone alone.

ARRY-520

Dr. Jatin Shah from M.D. Anderson Cancer Center in Houston then presented results from a Phase 2 study of ARRY-520 (abstract; presentation slide deck (pdf) made available by Dr. Shah as a courtesy to the Beacon’s readers).

Array BioPharma (NASDAQ: ARRY) is developing ARRY-520.  The drug inhibits kinesin spindle protein, which plays an important role in actively dividing cells.  It is being studied alone and in com­bi­na­tion with other drugs for several blood cancers.

The study included 32 myeloma patients who were treated with ARRY-520.  Their median age was 65 years, and they had received a median of six pre­vi­ous lines of ther­apy.  In addi­tion, 18 patients were treated with ARRY-520 plus dexamethasone (Decadron).  The median age of these patients was 67 years, and they had received a median of 10 pre­vi­ous lines of ther­apy.  All patients also received granulocyte colony-stimulating factor.

Among those treated with only ARRY-520, 16 per­cent achieved a partial response.  Among those treated with ARRY-520 plus dexa­meth­a­sone, 22 per­cent achieved a partial response.

The median duration of response was 8.6 months for ARRY-520 alone and 5.4 months for ARRY-520 plus dexa­meth­a­sone.

The researchers found that patients who responded to the ARRY-520-based ther­apy had low levels of a protein called apha-1-acid glycoprotein in the blood compared to patients who did not respond to treat­ment.

The most common severe side effects of ARRY-520 were low white blood cell counts (47 per­cent), low platelet counts (47 per­cent), low red blood cell counts (37 per­cent), fatigue (15 per­cent), low potassium levels (6 per­cent), and back pain (6 per­cent).  When dexa­meth­a­sone was added, addi­tional severe side effects included pneu­monia (20 per­cent), joint pain (5 per­cent), and upper res­pira­tory tract in­fec­tion (5 per­cent).

Given that patients receiving the com­bi­na­tion were significantly more heavily pretreated than the patients treated only with ARRY-520, yet were more likely to respond to treat­ment, Dr. Shah suggested that the com­bi­na­tion should be further studied.

Pomalidomide Plus Low-Dose Dexamethasone

The final talk of the session was another one about poma­lido­mide.  In this talk, Dr. Sundar Jagannath from Mount Sinai Medical Center in New York City presented results from a Phase 2 study of poma­lido­mide plus low-dose dexa­meth­a­sone (abstract).

The study included 221 re­lapsed and refractory myeloma patients who had received a median of 5 pre­vi­ous lines of ther­apy.  Half were treated initially with poma­lido­mide alone, while the other half were treated with poma­lido­mide plus low-dose dexa­meth­a­sone.  Patients treated with poma­lido­mide alone who re­lapsed could add dexa­meth­a­sone to their treat­ment regi­men.

The median age of the patients was 64 for those treated with poma­lido­mide plus dexa­meth­a­sone and 61 for those treated with poma­lido­mide alone.  Dr. Jagannath presented response rates and survival data for the entire study population, and he also broke the results out by age.

The over­all response rate was 34 per­cent for patients treated with poma­lido­mide plus dexa­meth­a­sone, 31 per­cent for those 65 years and younger and 37 per­cent for those above 65 years of age.

In contrast, the over­all response rate was 15 per­cent for patients treated with poma­lido­mide alone, 13 per­cent for those 65 years and younger and 18 per­cent for those above 65 years of age.

Although the response rates were higher for older patients, age had a negative impact on survival.  Among those treated with poma­lido­mide plus dexa­meth­a­sone, the median pro­gres­sion-free survival was 4.6 months over­all, 4.7 months for those 65 years and younger and 3.7 months for those above 65 years of age.  The difference in over­all survival was more notable with median over­all survival being 16.5 months over­all, 19.7 months for those 65 years and younger, but 11.8 months for those above 65 years of age.

For poma­lido­mide alone, the median pro­gres­sion-free survival was 2.6 months and the median over­all survival was 13.6 months.

The most common severe side effects were low white blood cell counts (41 per­cent), low red blood cell counts (22 per­cent), pneu­monia (22 per­cent), low platelet counts (19 per­cent), fatigue (14 per­cent), and shortness of breath (13 per­cent).  In addi­tion, 2 per­cent of patients developed blood clots.

Myeloma presentations from the rest of Day 3 as well as Day 4 of the ASH 2012 meeting also will be summarized in ASH daily updates to be published at The Beacon the next few days.  Additional coverage of key research results from the meeting will con­tinue throughout the rest of the week in individual, topic-specific news articles.  For all Beacon articles related to this year’s ASH meeting, see The Beacon’s full ASH 2012 coverage.