Results from a recent, small-scale study conducted at the MD Anderson Cancer Center in Houston suggest that three Velcade-based combination therapies given at lower doses over a short period of time may be safe and effective in newly diagnosed multiple myeloma patients .

In particular, two out of the three combinations showed overall response rates of above 90 percent, and all combinations were associated with few side effects.

Based on their findings, the researchers conclude that the tested combinations are viable alternatives to standard Velcade ^[1] (bortezomib)-based combinations given over longer periods of time, which can be associated with frequent side effects.

The researchers also recommend that the combinations be studied further in larger patient populations.  They are particularly interested in further study of Velcade in combination with Revlimid ^[2] (lenalidomide), cyclophosphamide ^[3] (Cytoxan), and dexamethasone ^[4] (Decadron), which appeared to be the most effective and safest combination among those tested.

According to the researchers, major advances have been made in the management of multiple myeloma in the past decade due to the use of novel agents, such as thalidomide ^[5] (Thalomid), Velcade, and Revlimid.

They added that rapid disease control continues to be a high priority in the management of the disease. Velcade-based initial therapies have been quite successful in this regard, with overall response rates of 85 percent to 90 percent in newly diagnosed patients.

However, the researchers note that the novel agent-based therapies have been associated with frequent – often serious – side effects, such as peripheral neuropathy (nerve damage that causes pain, tingling, and loss of sensation in the extremities), infections, and the formation of blood clots.

The researchers therefore sought to identify drug combinations that are as effective as current combina­tions, but less toxic, by administering the drugs in small doses over a short period of time.

They chose, in particular, to assess three different Velcade-based regimens due to the drug's efficacy and frequent use in myeloma therapies.

Between January 2010 and May 2012, the investigators treated 40 newly diagnosed myeloma patients with one of the following three combinations: Velcade- cyclophosphamide-dexamethasone (referred to as VCD or CyBorD), Velcade-Revlimid-Doxil ^[6] (liposomal doxorubicin)-dexamethasone (RVDD), or Velcade-Revlimid-cyclophosphamide-dexamethasone (RVCD).

The median patient age was 63 years, and 37 percent had Stage III disease based on the International Staging System scale.

The patients received no more than two cycles of initial treatment, and they could proceed to high dose therapy and stem cell transplant if they wished to and qualified for the procedure.

Each cycle of therapy lasted 28 days, but drug treatment occurred on only the first 11 days.

Velcade was administered on days 1, 4, 8 and 11 of the cycle, at 1.3 mg/m² in the VCD regimen, and 1.0 mg/m² in the other two regimens.  Revlimid was administered on days 1-11 at 25 mg per day. Dexa­metha­sone was administered on days 1-4 and 8-11 at 20 mg/m² per day.  Cyclo­phos­phamide was administered on days 1-4 of each cycle in the VCD and RVCD regimens, at 75 mg/m² twice daily in the VCD regimen and 60 mg/m² twice daily in the RVCD regimen.

Patients also were given 81 mg of aspirin per day to prevent the development of blood clots during treatment, and 500 mg per day of Valtrex (valacyclovir) to reduce chances of a shingles infection.

Overall, the investigators found that overall response rates (partial response or better) were high in all three treatment groups: 92 percent of patients in both the RVDD and RVCD treatment groups and 73 percent in the VCD group responded.

According to the researchers, these response rates are similar to those they observed in two other commonly used Velcade-based initial therapies they had investigated previously: Velcade-thalidomide-dexamethasone (87 percent) and Velcade-Revlimid-dexamethasone (89 percent).

The investigators also found that the safety profiles of the three combination therapies tested were favorable. They described the side effects as infrequent, mild, and reversible. The most common side effects included infections (16 percent), rash (13 percent), and constipation (13 percent).

Overall, the rate of side effects was much lower than observed in patients receiving Velcade combination regimens dosed over longer periods of time.

In particular, the rate of neuropathy of all grades was much lower in the three regimens in this study (13 percent). Furthermore, none of the three regimens in this study caused blood clots or severe neuropathy.

A total of 31 of the 40 patients treated with the three short-term combination regimens went on to receive high-dose chemotherapy followed by a stem cell transplant.  The procedure deepened response in the patients, in that seven of the patients who had only achieved a partial response prior to stem cell  transplantation went on to achieve a complete response after transplantation.

Two patients in the study died, one after 5 months and one after 14 months.  Both had achieved a partial response, but the responses were short-lived.  Neither patient went on to receive a stem cell transplant.

For more information, please refer to the study in Clinical Lymphoma, Myeloma and Leukemia ^[7] (abstract).