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Lorvotuzumab Mertansine Combination Effective In Relapsed/Refractory Multiple Myeloma Patients (ASH 2012)

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Published: Jan 4, 2013 3:54 pm

Results from an ongoing Phase 1 study demonstrate that lorvotuzumab mertansine in combination with Revlimid and dexamethasone is effective as a therapy for relapsed and refractory myeloma patients.

The updated trial results were presented by Dr. Jesus Berdeja from the Sarah Cannon Research Institute in Nashville, Tennessee, the American Society of Hematology (ASH) annual meeting in Atlanta last month.

Ten patients are currently continuing with the clinical trial. According to Dr. Berdeja, these interim results support the continued evaluation of the combination in relapsed and refractory myeloma patients. "This was a fairly heavily pre-treated population, and there were significant clinical benefits seen," said Dr. Berdeja.

However, comparison of the current trial results with those from other studies in a similar patient population suggest that lorvotuzumab mertansine may not add significantly to the effectiveness of Revlimid and dexamethasone used without the additional drug.

Initial results of the lorvotuzumab mertansine Phase 1 trial had been presented at last year’s meeting of the American Society of Clinical Oncology (see related Beacon news).

Lorvotuzumab mertansine (IMGN901) is being developed by ImmunoGen (NASDAQ: IMGN). It is a chemotherapy agent (mertansine) attached to an antibody (lovortuzumab) that directs the chemotherapy to the cancer cell.  The lorvotuzumab portion of the drug recognizes the CD56 protein found on the surface of myeloma cells.  Approximately 78 percent of myeloma patients have myeloma cells with the CD56 protein.

According to Dr. Berdeja, lorvotuzumab mertansine has demonstrated encouraging single-agent activity in a previous Phase 1 study. In addition, preclinical studies have shown that lorvotuzumab mertansine combined with Revlimid (lenalidomide) and dexamethasone (Decadron) is significantly more effective than Revlimid plus dexamethasone alone.

In this study, researchers sought to determine the efficacy and safety of lorvotuzumab mertansine in combination with Revlimid and dexamethasone in pre-treated myeloma patients. The study included 44 relapsed and/or refractory patients with a median age of 63 years. Patients had received a median of two prior regimens; 91 percent had received prior Velcade (bortezomib), and 75 percent had received prior Revlimid or thalidomide (Thalomid).

Each patient received 25 mg of Revlimid on days 1 to 21 and 40 mg of dexamethasone on days 1, 8, 15, and 22 of a 28-day treatment cycle. Patients also received variable doses of lorvotuzumab mertansine (75 mg/m2, 90 mg/m2, 112 mg/m2) intravenously on days 1, 8, and 15. Overall, 77 percent of patients received the lowest dosage of lorvotuzumab mertansine.

Of 39 evaluable patients, 57 percent responded to the treatment, including 3 percent who reached a stringent complete response, 28 percent who reached a very good partial response, and 26 percent who reached a partial response.

Thirty-two percent of patients involved in the study had no prior exposure to Revlimid. Of these patients, 88 percent responded to treatment, including 6 percent who achieved a stringent complete response, 50 percent who reached a very good partial response, and 31 percent who reached a partial response.

The median time to progression among patients treated with 75 mg/m2 of lorvotuzumab mertansine was 7.7 months.

Other studies of two- or three-drug combinations in myeloma patients with two or more prior therapies have reported response rates similar to, or higher, than the 57 percent response rate seen in the current study.

A retrospective study conducted by French researchers, for example, reported an overall response rate of 62 percent for older myeloma patients with two previous therapies who were treated with just Revlimid and dexamethasone (see related Beacon news).

A Phase 1b study of elotuzumab, Revlimid, and dexamethasone in patients with a median of three previous therapies reported an overall response rate of  82 percent (see related Beacon news).

And, finally, a Phase 3 trial of Zolinza (vorinostat) and Velcade (bortezomib) – without any dexamethasone – in patients with a median of two previous therapies reported an overall response rate of 57 (see related Beacon news).  The comparator arm of the same trial, where patients were treated with just Velcade, had a response rate of 41 percent.

In the current study involving lorvotuzumab mertansine combined with Revlimid and dexamethasone, the most common side effects of all grades (mild to severe) included peripheral neuropathy (tingling, pain, and loss of sensation in the extremities) (56 percent), fatigue (41 percent), low white blood cell counts (32 percent), low platelet counts (32 percent), nausea (29 percent), and diarrhea (26 percent).

For more information, please see abstract 728 on the ASH 2012 meeting website as well as Dr. Berdeja's presentation slides, which he has made available for download and viewing as a courtesy to the Beacon’s readers

Photo by IndyDina with Mr. Wonderful on Flickr - some rights reserved.
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