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Celgene International announce Revlimid data at ASH 2009


Celgene International announced that data evaluating continuous therapy with REVLIMID (lenalidomide) across all stages of multiple myeloma were presented during the 51st American Society of Hematology’s annual meeting in New Orleans, LA.

The studies demonstrated REVLIMID has significant clinical potential in active newly diagnosed myeloma, for induction therapy followed by continuous treatment and in asymptomatic smoldering multiple myeloma.

Over the past decade, the treatment landscape for myeloma has evolved dramatically with the advent of novel treatment agents such as REVLIMID. Initially used for relapsed or difficult-to-treat cases, novel agents are being increasingly tested as early treatment options[1] <#_ftn1> . New clinical studies presented this week support the use of continuous therapy throughout progression of the disease as a treatment strategy improving outcomes.

“These studies demonstrate that at all stages of multiple myeloma, sustained diseases control can be achieved by continuous treatment with Revlimid said lead investigator Antonio Palumbo, MD, University of Turin.”Demonstrating that continuous Revlimid-based treatment is as effective as a stem cell transplant is great news for patients because it provides another treatment option which is safer and more convenient as an oral therapy”.

REVLIMID in newly diagnosed active myeloma A landmark phase III study lead by Antonio Palumbo, MD, University of Turin, assessed REVLIMID in elderly patients with newly diagnosed, active myeloma. This three-arm study compared two regimens with fixed treatment duration, melphalan and prednisone and melphalan, prednisone plus REVLIMID (MPR), to melphalan, prednisone plus REVLIMID followed by continuous REVLIMID (MPR+R).

The study showed that continuing treatment with Revlimid (MPR+R) reduced the risk of progression or death by 50% compared to treatment with fixed duration MP. Continuing treatment with Revlimid alone after MPR induction (MPR+R) showed a 75% reduction in risk of progression versus fixed duration MPR demonstrating the value of continuous treatment in achieving sustained control of the disease.

Adverse events experienced by patients in the study included neutropenia, thrombocytopenia, gastrointestinal disorders, deep-vein thrombosis, fatigue and rash. No Grade 3 or 4 peripheral neuropathy was noted. In the continuous treatment period Grade 3 or 4 adverse events were minimal.

REVLIMID compared to autologous stem cell transplant in multiple myeloma

Also lead by Antonio Palumbo, MD, University of Turin, a phase III study compared melphalan, prednisone and REVLIMID (MPR) with autologous stem cell transplant in patients with multiple myeloma under 65 years old. All patients were treated with REVLIMID and low dose dexamethasone for induction therapy. Following a second randomisation, patients then received continuous low-dose Revlimid treatment or no further therapy. In an additional sub-study, patients were randomised to receive preventative aspirin or low molecular heparin in order to prevent thromboembolic events.

The results of this early analysis indicated that at 12 months both treatments resulted in over 91% progression free survival, suggesting that MPR is equally effective as compared to autologous stem cell transplants in this patient population. There was no significant difference in the response rates of patients with high-risk cytogenetics. During consolidation (MPR versus transplant), complications were significantly higher with patients who were treated with stem cell transplants, including higher incidences of grade 3-4 neutropenia, thrombocytopenia, infections and gastrointestinal toxicities.

Aspirin was equally effective as low molecular heparin in preventing thromboembolic events. Additionally, patients were able to collect adequate stem cells post-treatment with the median number of stem cells yielded 10 x106 s; and 94% of patients collected the minimum dose of stem cells, which was 2×106/kg.

During induction with REVLIMID and dexamethasone, the most frequent grade 3-4 adverse events were neutropenia, anaemia, infections, skin rash, fatigue and thromboembolic events.

REVLIMID in smoldering myeloma
Another randomised phase III study evaluated whether early treatment with  REVLIMID and dexamethasone prolongs time to disease progression (to symptomatic disease) compared to no treatment for patients with high-risk smoldering multiple myeloma, who show no overt symptoms and thus are presently only treated once they develop symptoms. Patients were treated with REVLIMID and dexamethasone as induction therapy for nine four-week cycles and then continued treatment with a lower dose of REVLIMID to sustain disease control until disease progression. The results showed a 81% percent response rate, including 51 percent partial response, 16 percent very good partial response, and 14 percent complete response. For the 16 patients who completed all nine treatment cycles, the response rate was 91 percent.

After a median follow-up of 14 months, disease progression was observed in two patients (4%) treated with REVLIMID and dexamethasone, while sixteen (34%) patients progressed to active myeloma in the arm with no treatment.  Ten out of 16 of those patients also developed bone lesions due to active myeloma.

Revlimid and dexamethasone has been able to induce CRs and prolong the TTP with a manageable and acceptable toxicity profile. No Grad 4 toxicities were observed. Grade 3 adverse events in patients treated with REVLIMID and dexamethasone included anaemia and asthaenia. Serious adverse events include included infection, gastrointestinal bleeding pancreatitis and delirium.  One patient discontinued treatment because of adverse events.  Dose adjustments were made as necessary to manage toxicity.

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