Revlimid Clinical Studies - Lenalidomide Clinical Studies


What have Revlimid clinical studies shown?

Revlimid® (lenalidomide, Celgene) clinical studies have shown improved survival in patients with newly diagnosed/untreated myeloma.

Is Revlimid-dex effective in previously untreated myeloma?

The combination of Revlimid and dexamethasone is an effective therapy for patients with myeloma, including those who are eligible for stem cell transplant and those who are not. One study showed that Revlimid plus high-dose dex was more effective than high-dose dex alone.[Zonder Blood 2007 abstract] Another important study showed that patients taking Revlimid plus low-dose dex had significantly improved survival and fewer side effects than patients taking Revlimid plus high-dose dex [Rajkumar Lancet Oncol 2010].

  • In this study, 96% of patients taking Revlimid low-dose dex were alive at 1 year and 87% were alive at 2 years.
  • There was no difference in survival time between patients who went on to high dose chemotherapy plus stem cell transplant and those who took Revlimid plus low-dose dex for an extended period of time (more than 4 months). Similar results were seen regardless of age.
  • During the first 4 months of treatment, the incidence of serious (grade 3/4) side effects was lower with Revlimid plus low-dose dex versus Revlimid plus high-dose dex (35% versus 52%).

The FDA approval for use of Revlimid in newly diagnosed myeloma was based on the results of the large Phase III FIRST™ Trial. This study compared 3 different treatments in myeloma patients who were not candidates for stem cell transplant: continuous Revlimid-low-dose dex until disease progression, a fixed course of Revlimid-low-dose dex (18 cycles), and the combination of melphalan, prednisone, and thalidomide [Benboubker NEJM 2014].

  • In this study, patients receiving continuous Revlimid-low-dose dex had a 28% reduction in the risk of disease progression or death compared with patients treated with MPT, and a 30% reduction compared with the fixed course of Revlimid-low-dose dex. Time to disease progression was 25.5 months compared to 21.2 months and 20.7 months, respectively.
  • An interim analysis showed that overall survival was also longer in the group receiving continuous Revlimid-low-dose dex (58.9 months) compared to 48.5 months in the MPT group and 56.7 months in the fixed Revlimid-low-dose dex group.

Is Revlimid-Velcade-dex effective in previously untreated myeloma?

Revlimid is thought to make myeloma cells more sensitive to Velcade® (bortezomib, Takeda Oncology) and dexamethasone. The combination of Revlimid, Velcade, and dexamethasone (RVD or VRD) has been shown to be very effective as frontline therapy, with unprecedented activity seen, even in patients with high-risk features. In some cases, a lower dose of dexamethasone is used and the combination is referred to as VRd or RVd.

  • For example, data from a large Phase III study (SWOG S0777) in patients with previously untreated myeloma showed that the addition of Velcade to Revlimid-low-dose dexamethasone (Rd) improved survival.
    • The study included 525 patients, including those who were transplant-eligible and those who were not transplant candidates. All patients received Rd maintenance until their disease progressed or they experienced unacceptable toxicity
    • Patients receiving VRd experienced a significantly longer time before their disease progressed (progression-free survival, PFS) compared to Rd (43 vs. 30 months).
    • Overall survival was significantly longer in patients receiving VRd compared to Rd (75 vs. 64 months).
  • Performing a stem cell transplant early after RVd induction therapy was shown to improve progression-free survival over RVd induction alone in a large Phase III study (IFM/DFCI 2009).
    • The study included 700 newly diagnosed patients who were eligible for stem cell transplantation. All received RVd induction and half also received an autologous stem cell transplant. All patients then received Revlimid maintenance for 1 year.
    • On average, patients who received a transplant experienced longer PFS (43 vs 34 months) and the percentage of patients surviving without disease progression at 4 years was significantly higher (47% vs. 35%).
    • Among responding patients in either treatment arm, PFS was significantly longer in those who had no evidence of remaining myeloma cells present in the bone marrow (minimal residual disease, MRD) before and after maintenance therapy as detected by very sensitive tests.
    • Patients on this study continue to be followed to determine the effect of transplant on overall survival.

RVD is included in myeloma treatment guidelines as one of several preferred options for initial therapy for transplant candidates, and is one of the most commonly used regimens in transplant candidates in the United States. RVD is also one of several preferred options for treating myeloma in patients who are not transplant candidates.

What other Revlimid combination therapies are effective in previously untreated myeloma?

Revlimid-low-dose dexamethasone (Rd) is being evaluated in Phase III studies in combination with a variety of newer agents for treatment of patients with newly diagnosed myeloma.

  • Rd in combination with Empliciti™ (elotuzumab, Bristol-Myers Squibb) is being evaluated in the ELOQUENT-1 trial.
  • Rd in combination with Ninlaro® (ixazomib, Takeda Oncology), or IRd, is being evaluated in the TOURMALINE-MM2 trial.
    • A Phase I/II trial evaluating this combination showed a 92% overall response rate, with 58% of patients achieving a very good partial response rate or better, including a complete response (CR)/stringent CR rate of 27%.
    • Based on these results, IRd is listed as an option for initial therapy in myeloma treatment guidelines.

Is Revlimid effective as maintenance therapy following high dose chemotherapy and stem cell transplantation?

Two large studies have shown that patients who received Revlimid as maintenance therapy following high-dose chemotherapy and stem cell transplantation have a significantly longer remission time compared with those who did not receive any maintenance treatment. Revlimid maintenance therapy was taken at a dose of 10-15 mg/day in these studies—which is lower than the typical dose of 25 mg/day.

One study, conducted in the United States, showed that maintenance therapy with Revlimid significantly prolonged the time until disease progression. In addition, the overall survival rate was higher for patients who received Revlimid. This is the first study to show a survival benefit with Revlimid maintenance therapy.

The other study, conducted in France, showed that in patients who received Revlimid as maintenance therapy, there were fewer patients who had progression of their myeloma after 3 years of follow-up. However, in this study there has been no improvement in the overall survival among those receiving Revlimid.

There was a small increase in second new cancers in these studies, which did not affect the overall benefit of Revlimid on disease progression. Thus, some researchers believe that the benefits of maintenance therapy with Revlimid may outweigh the risks of a second new cancer.

Patients who have undergone a stem cell transplant should discuss with their doctors the pros and cons of maintenance therapy with Revlimid.

Is Revlimid-dex effective in treating relapsed or refractory myeloma?

Two large clinical trials showed that Revlimid-high-dose-dex is significantly more effective than high-dose dexamethasone in treating relapsed or refractory myeloma. Over 700 patients throughout the world participated in these studies.

Revlimid-dex significantly delayed disease progression and extended survival. Response rates were superior with Revlimid-dex as well:

  • Patients receiving Revlimid-dex lived nearly 3 years.
  • Those who received Revlimid-dex right after initial remission lived longer than those who received Revlimid-dex after 2 or more therapie.
  • Overall responses were nearly 3 times that seen with dexamethasone, with a high rate of complete responses (CR).

Is Revlimid-Velcade-dex effective in treating relapsed or refractory myeloma?

Results from a multicenter Phase II trial show that the combination of Revlimid, Velcade, and dexamethasone is very effective as a treatment for relapsed or refractory myeloma. As a result, RVD is often used in this setting and is listed as one of several preferred options for treatment of relapsed or refractory myeloma in current treatment guidelines.

  • Overall, 64% of 64 evaluable patients responded to this treatment (a partial response or better) and 25% achieved a complete or near-complete response.
  • After a median follow-up of almost 36 months, overall survival was encouraging and approached 30 months, and 45% of patients were still alive.
  • The combination was well tolerated, with manageable side effects

What Revlimid combination therapies are effective in relapsed and/or refractory myeloma?

Revlimid is commonly used as part of combination therapy for the treatment of relapsed and/or refractory myeloma. Recent clinical trials have shown that, as with RVD, adding a third agent to Revlimid-dex improves outcomes over that seen with Revlimid-dex alone.

Three myeloma drugs have been evaluated in combination with Revlimid-low-dose dexamethasone (Rd) in Phase III clinical trials in patients who had received one to three prior therapies. Results of these studies supported the approval of these drugs for use in the treatment of myeloma and they are listed as preferred regimens in myeloma treatment guidelines.

  • Kyprolis® (carfilzomib, Onyx Pharmaceuticals) and Revlimid-low-dose dex (KRd)
    • The ASPIRE trial included 792 patients and compared KRd with Rd.
    • Patients receiving KRd lived 50% longer (8.7 months longer) without their disease worsening compared to patients receiving Rd alone.
    • Progression-free survival was 26.3 months in the KRd group compared to 17.6 months in the Rd group.
    • The overall response rate was 87% in the KRd group and 67% in the Rd group.
    • A higher percentage of patients in the KRd group achieved a stringent complete response (sCR) than in the Rd group (14% vs. 4%).
  • Empliciti™ (elotuzumab, Bristol-Myers Squibb) and Revlimid-low-dose dex
    • The ELOQUENT-2 trial included 646 patients and evaluated Rd with and without Empliciti.
    • The addition of Empliciti to Rd resulted in a 30% reduction in risk of disease progression or death compared to Rd alone.
    • On average, the time that patients receiving Empliciti-Rd lived without their disease worsening was 19.4 months compared with 14.9 months with Rd.
    • This significant progression-free survival benefit with Empliciti-Rd was maintained over time, with higher rates compared with Rd at one year (68% vs. 57%), two years (41% vs. 27%), and three years (26% vs. 18%).
    • In addition, a significantly higher percentage of patients taking Empliciti with Rd achieved a partial response or better compared to those only taking Rd (overall response rate of 79% vs. 66%).
  • Ninlaro® (ixazomib, Takeda Oncology) and Revlimid-low-dose dex (IRd)
    • The TOURMALINE-MM1 trial included 722 patients and compared IRd with Rd.
    • On average, patients receiving IRd significantly longer without their disease worsening compared to patients receiving Rd (20.6 months vs. 14.7 months).
    • Responses lasted longer when Ninlaro was added (20.5 months vs.15 months with Rd).
    • The overall response rate was higher with IRd compared with Rd (78% vs. 72%) and the complete response rate was also higher (12% and 7%, respectively).

How is Revlimid currently being studied in myeloma?

Revlimid is being evaluated in a number of ongoing clinical trials in newly diagnosed and relapsed and/or refractory myeloma, as well as in patients with asymptomatic high-risk smoldering multiple myeloma to see if it can delay progression to active myeloma.

For example, Revlimid-low-dose dex is being tested in Phase III trials in newly diagnosed myeloma in combination with a variety of agents, including:

  • Darzalex™ (daratumumab, Genmab), a monoclonal antibody that binds to the CD38 marker on myeloma cells
  • Keytruda® (pembrolizumab, Merck), a type of immunotherapy known as a checkpoint inhibitor
  • Velcade or Kyprolis® (carfilzomib, Onyx)

The combination of Revlimid, Velcade, and low-dose dex (RVd) is being evaluated alone and in combination with high-dose chemotherapy and autologous stem cell transplant in a Phase III trial in newly diagnosed myeloma. Results from this trial will help determine if transplant is still necessary in the initial management of myeloma in younger patients or whether novel agents alone provide similar outcomes.

Interested in learning more about Revlimid clinical trials? Talk to an MMRF Patient Support Nurse to learn more or use our clinical trials finder: