Results from a Phase 1 study indicate that tabalumab in combination with Velcade demonstrates both efficacy and safety in myeloma patients who have relapsed after several previous therapies.

Dr. Nooper Raje from Massachusetts General Hospital in Boston presented the results of the study at the American Society of Hematology (ASH) annual meeting earlier this month. She explained that tabalumab was very promising in this particular patient population, and added that “this was a very well tolerated regimen.”

However, Dr. Raje emphasized that further study of tabalumab at higher doses and in combination with other drugs was still needed to confirm the drug's efficacy and safety profile.

The results Dr. Raje presented at the ASH meeting were from a clinical trial testing different doses of tabalumab ^[1].  This makes it difficult to assess how effective the tabalumab-Velcade ^[2] (bortezomib) combination is in comparison to other treatment options for relapsed myeloma patients.

That said, the initial results for the tabalumab-Velcade combination suggest it may not be quite as effective as other potential combination therapies which are in more advanced stages of development.

Tabalumab (also known as LY2127399 ^[3]) 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, a type of white blood cell that includes plasma cells.

Tabalumab has been tested as a potential treatment for a number of medical conditions in addition to multiple myeloma, including rheumatoid arthritis, lupus, and multiple sclerosis.  Several clinical trials of the drug in rheumatoid arthritis were recently suspended, however, because the drug was not showing sufficient effectiveness in treating that condition.

As for multiple myeloma, preclinical studies have indicated tabalumab is active against the disease, and it also may help prevent bone destruction.

According to Dr. Raje, one reason tabalumab is interesting as a potential anti-myeloma therapy is because research has shown that BAFF levels are elevated in multiple myeloma patients compared to healthy people.

In the study discussed at the recent ASH meeting, Dr. Raje and her colleagues investigated the efficacy and safety of tabalumab in combination with Velcade in relapsed and refractory multiple myeloma patients.

The study included 48 multiple myeloma patients with a median age of 66 years who had received a median of three prior therapies.  Previous therapies included Revlimid ^[4] (lenalidomide) or thalidomide ^[5] (Thalomid) (88 percent of patients) and Velcade (75 percent).  In addition, 52 percent of the patients had received at least one stem cell transplant.

Three-quarters of the patients in the study received between 1 mg and 300 mg of tabalumab once every three weeks along with 1.3 mg/m² of Velcade. The remaining quarter also received 20 mg of dexamethasone ^[6] (Decadron), administered orally eight times over the course of each three-week cycle. The main reason, according to Dr. Raje, for adding dexamethasone is that it is common clinical practice to administer Velcade in combination with dexamethasone.

All patients received a median of 5.5 treatment cycles.

The overall response rate was 46 percent, with 4 percent achieving complete response, 8 percent achieving very good partial response, and 33 percent achieving a partial response. In addition, 44 percent of the patients had stable disease.

Dr. Raje pointed out that patients with BAFF levels of less than 1,500 pg/mL were more likely to respond to tabalumab than those with higher BAFF levels.

The median duration of response in responding patients was 7.3 months, and the median time to disease progression was 4.9 months.

The overall response rate (46 percent) for the tabalumab-Velcade combination appears to be somewhat lower than one might expect for a combination regimen tested in myeloma patients with a median of three previous therapies.

This is partly to be expected, since the results are from a Phase 1 trial that tested a wide range of different dose combinations to determine the optimal dosing.

That said, a Phase 1 trial which tested several different doses of elotuzumab ^[7] in combination with Revlimid and dexamethasone in myeloma patients with a median of three previous treatments yielded an overall response rate of 82 percent (see related Beacon ^[8] news).

In addition, two Phase 2 trials whose results were presented at the recent ASH meeting involved patients with even more previous therapies than the patients in the tabalumab-Velcade trial, yet the other combinations showed higher overall response rates.

The combination of Kyprolis ^[9] (carfilzomib), pomalidomide ^[10], and dexamethasone, for example, was tested in myeloma patients with a median of six previous therapies, and the overall response rate was 50 percent (see related Beacon ^[11] news article).

Similarly, the combination of clarithromycin ^[12] (Biaxin), pomalidomide, and dexamethasone was tested in myeloma patients with a median of five previous therapies, and it had an overall response rate of 57 percent (see related Beacon ^[11] news article).

As for the side effects of the tabalumab-Velcade combination, Dr. Raje reported during her presentation that the therapy was was well tolerated.

The most common severe side effects included low platelet counts (23 percent), peripheral neuropathy (pain, tingling, or less of sensation in the extremities) (13 percent), pneumonia (13 percent), and low white blood cell counts (10 percent).

Two of the 48 patients died during the study. One death was attributed to progression of the patient's myeloma.  The other death occurred in a patient whose myeloma also was progressing.  However, the death -- which was due to respiratory failure -- was categorized as a adverse reaction to treatment.

Dr. Raje pointed out that, based on the findings of this study, a Phase 2 study of tabalumab has been initiated. The study will test tabalumab at two different doses (100 mg and 300 mg) in combination with Velcade and dexamethasone, as compared to Velcade plus dexamethasone alone.

For more information, please refer to abstract 447 ^[13] on the ASH 2012 meeting website as well as Dr. Raje's presentation slides ^[14], which she and Eli Lilly have made available for download and viewing as a courtesy to The Beacon’s readers.