daratumumab subcutaneous injection (Darzalex) is accepted for use within NHSScotland....in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.

Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President, Representative Director, Gyo Sagara; “ONO”) announced today that an additional twice-weekly regimen has been available for KYPROLIS® (generic name: carfilzomib) for Intravenous Injection 10 mg and 40 mg (“KYPROLIS”), a proteasome inhibitor, in Japan, in combination with dexamethasone plus Darzalex® (generic name: daratumumab) Intravenous Infusion, a human anti-CD38 monoclonal antibody (“Darzalex”) (DKd) for the approved indication of relapsed or refractory multiple myeloma...based on the result of a global, multicenter, randomized, open-label Phase III study, CANDOR study...

Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the Ministry of Health, Labor and Welfare (MHLW) in Japan has approved the use of DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma.

Darzalex is a cancer medicine used to treat adults with multiple myeloma (a cancer of the bone marrow). In patients with newly diagnosed multiple myeloma it is used...in combination with the medicines lenalidomide and dexamethasone or with bortezomib, melphalan and prednisone in patients who cannot have autologous stem cell transplant (a transplant of the patient’s own blood-producing cells). Bortezomib, lenalidomide and melphalan are used for treating multiple myeloma and dexamethasone and prednisone suppress the immune system

Darzalex is indicated:...as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.

DARZALEX is a CD38-directed cytolytic antibody indicated for the treatment of adult patients with multiple myeloma:...as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent....in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy...in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant....in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy

DARZALEX is a CD38-directed cytolytic antibody indicated for the treatment of adult patients with multiple myeloma...as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.

Multiple Myeloma: The following regimens were moved from Other Recommended to Preferred Regimens…Daratumumab/carfilzomib/dexamethasone... Multiple Myeloma: Therapy for previously treated multiple myeloma…Other Recommended Regimens...Daratumumab/cyclophosphamide/bortezomib/dexamethasone… …the NCCN Panel has included daratumumab/bortezomib/melphalan/prednisone as a category 1 option for treatment of patients with newly diagnosed MM not eligible for HCT

Multiple Myeloma: Therapy for previously treated multiple myeloma...Useful In Certain Circumstances…Daratumumab

In this subgroup analysis of OCTANS and ALCYONE, the prolonged PFS observed with D-VMP vs VMP in the overall study populations was maintained irrespective of the achievement of MRD negativity or the presence of high cytogenetic risk...These results further support the use of daratumumab in combination with VMP in both Asian and global patients with TIE NDMM.

With a median follow-up of >3 years, this final analysis of OCTANS demonstrated a continued clinical benefit with D-VMP versus VMP in Asian patients, with PFS improvement comparable to that observed in the global ALCYONE study (HR, 0.35 vs 0.42, respectively). No new safety concerns were identified for D-VMP with extended follow-up.

In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients...After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001)...D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients.

At a median (range) follow-up of 72.6 months (0.0-79.8), significant OS benefit was observed with D-Vd (hazard ratio, 0.74; 95% CI, 0.59 to 0.92; P = .0075). Median OS was 49.6 months with D-Vd versus 38.5 months with Vd. Prespecified subgroup analyses demonstrated an OS advantage with D-Vd versus Vd for most subgroups...D-Vd significantly prolonged OS in patients with RRMM, with the greatest OS benefit observed in patients with one prior line of therapy.

In this updated analysis of ALCYONE, the addition of DARA to VMP continued to prolong OS versus VMP alone in transplant-ineligible patients with NDMM; median OS was reached in both arms for the first time after a median follow-up of >6 years. D-VMP also achieved a 4-fold higher MRD-negativity rate and a 5-fold higher ≥12-month sustained MRD-negativity rate versus VMP alone. No new safety concerns were observed with longer follow-up. Our results continue to support the use of D-VMP in transplant-ineligible patients with NDMM.

In conclusions, this study provides a clear proof of beneficial effects of daratumumab-based therapy in patients with relapsed or refractory MM with an acceptable safety profile. The progression-free survival benefit was consistent regardless of patient's baseline characteristics or previous therapy agents.

After median follow-up of approximately 17 months, median progression-free survival was not reached in the KdD group versus 15·8 months in the Kd group (hazard ratio 0·63; 95% CI 0·46–0·85; p=0·0027). Median treatment duration was longer in the KdD versus the Kd group (70·1 vs 40·3 weeks)....KdD significantly prolonged progression-free survival versus Kd in patients with relapsed or refractory multiple myeloma and was associated with a favourable benefit–risk profile.

Among 1 PL pts, median PFS was 27.0 vs 7.9 mo (HR, 0.21; 95% CI, 0.15-0.31, P <0.0001) for D-Vd vs Vd….PFS2 was also significantly prolonged with D-Vd vs Vd in 1 PL pts (median: not reached vs 23.4 mo; HR, 0.34, 95% CI, 0.24-0.49; P <0.0001; Figure 1B); 42-mo PFS2 rates were 58% vs 19%, respectively....In this updated analysis of CASTOR, D-Vd maintains significant PFS and ORR benefits in RRMM, with the greatest benefit achieved by pts who received 1 PL of therapy.

In this two-part, randomised, open-label, phase 3 CASSIOPEIA trial, we recruited transplant-eligible patients with newly diagnosed multiple myeloma...157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010)....D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety.

Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001)...After 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile.