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The median PFS was not reached in the D-VMP group and was 18.1 months in the VMP group ( ranges not provided ). “ The PFS treatment benefit of D-VMP versus VMP was consistent across all prespecified subgroups , including age ≥75 years , ISS stage III , and high-risk cytogenetics ,” the authors noted . See TABLE 2 for all treatment outcomes .

The benefit appeared to be driven by deeper responses in the D-VMP group , according to Dr . San-Miguel .

More patients in the D-VMP group attained minimal residual disease ( MRD ) - negative status compared to patients in the control group ( 22.3 % vs . 6.2 %; HR = 4.36 ; 95 % CI 2.64-7.21 ; p < 0.0001 ).

“ We know now that [ MRD ] has become probably the most relevant marker for prognosis in MM ,” Dr . San- Miguel said . “ As we saw in the PFS curve , patients achieving MRD-negative status – in the non-daratumumab arm , as well as the daratumumab arm ( in which MRDnegativity was three times easier to obtain ) – show a significantly longer PFS .”

Toxicity profiles were similar between study cohorts , Dr . San-Miguel reported , except for the high incidence of any-grade upper respiratory tract infection ( 26.3 % vs . 13.8 %) and grade 3 / 4 pneumonia ( 11.3 % vs . 4.0 %) in the D-VMP group .

Other common any-grade treatmentrelated adverse events ( AEs ) occurring in the D-VMP and VMP groups included neutropenia ( 49.7 % vs . 52.5 %), thrombocytopenia ( 48.8 % vs . 53.7 %), anemia ( 28.0 % vs . 37.6 %), and peripheral sensory neuropathy ( 28.3 % vs . 34.2 %). Common grade 3 / 4 AEs included neutropenia ( 39.9 % vs . 38.7 %), thrombocytopenia ( 34.4 % vs . 37.6 %), and anemia ( 15.9 % vs . 19.8 %).

One patient in each cohort discontinued treatment because of pneumonia . Grade 3 / 4 infections occurred in 23.1 percent of patients in the D-VMP cohort and 14.7 percent of the VMP cohort ; these infections led to treatment discontinuation in 0.9 percent and 1.4 percent of patients , respectively .

Infusion-related reactions from daratumumab appeared in 27.7 percent of patients , “ but occurred mainly in the first course of treatment , and were usually grade 1 or 2 ,” he added . Tumor lysis syndrome occurred in 1 percent of patients in each arm , and second primary malignancy occurred at similar rates ( 2.3 % for D-VMP and 2.5 % for VMP ).

When asked if the results from ALCYONE are strong enough to potentially replace AHCT with the D-VMP combination , Dr . San-Miguel said the goal is instead to expand treatment choices for all patients with MM . “ Use of monoclonal antibodies is going to challenge the role of transplant ,” he explained . “ Nevertheless , our goal is to cure MM , and we want to use all possible treatments to achieve this goal .”

The study ’ s findings are limited by the open-label design , which may have introduced bias . Overall survival data were also not presented . Dr . San-Miguel added that the results may not be generalizable to the U . S . patient population , where VMP is not the standard of care for newly diagnosed , transplant-ineligible patients .

The authors report financial relationships with Takeda , Amgen , Celgene , and Janssen , which provided funding support for the study .

REFERENCE

Mateos MV , Dimopoulos MA , Cavo M , et al . Phase 3 randomized study of daratumumab plus bortezomib , melphalan , and prednisone ( D-VMP ) versus bortezomib , melphalan , and prednisone ( VMP ) in newly diagnosed multiple myeloma ( NDMM ) patients ( Pts ) ineligible for transplant ( ALCYONE ). Abstract LBA-4 . Presented at the 2017 American Society of Hematology Annual Meeting , December 12 , 2017 ; Atlanta , GA .

TABLE 2 . Overall Response and MRD Negativity Rate

MRD = minimal residual disease ; D-VMP = daratumumab , bortezomib , melphalan , prednisone ; ORR = overall response rate ; CR = complete response ; VGPR = very good partial response ; PR = partial response

Because many hospice organizations disallow life-extending transfusion support , transfusion dependence ( TD ) can pose a substantial barrier to enrolling patients with leukemia in palliative or end-of-life ( EOL ) services , according to a report presented at the 2017 ASH Annual Meeting . When these patients are enrolled , they spend about half as much time receiving hospice care as patients who do not require transfusions .

Adam J . Olszewski , MD , from the Alpert Medical School of Brown University in Providence , Rhode Island , and colleagues evaluated the association between TD ( defined as requiring ≥2 transfusions in the 30 days before death or hospice enrollment ) and EOL outcomes among Medicare beneficiaries diagnosed with acute and chronic leukemias between 1996 and 2011 and who died between 2001 and 2011 ( at least 30 days after diagnosis ).

Among the 21,076 eligible patients ( median age = 79 years ; range not provided ) identified from the Surveillance , Epidemiology , and End Results ( SEER ) -Medicare database , 20 percent were transfusion dependent before death or hospice enrollment . Patients in this group were significantly younger , mostly men , and more often had acute leukemia , the researchers noted .

Between 2001 and 2011 , use of hospice at EOL increased in the entire leukemia population , from 35 percent to 49 percent ( p < 0.0001 for trend ). Compared with those not enrolled in hospice , enrollees had a lower likelihood of inpatient death ( 3 % vs . 75 %; p value not provided ), chemotherapy use in the last 14 days of life ( 5 % vs . 16 %; p value not provided ), and lower median Medicare spending at EOL ($ 7,662 vs . $ 17,783 ; p value not provided ).

Surprisingly , enrollment was higher among patients with TD than without ( 47 % vs . 43 % p < 0.0001 ); after adjusting for age , sex , time from diagnosis , and other baseline characteristics , patients with TD were 7 percent more likely to receive hospice ( relative risk [ RR ] = 1.07 ; 95 % CI 1.03-1.11 ).

However , that slight increase did not translate into “ meaningful use ” of hospice care , the authors reported . For example , the median time on hospice was nine days ( range not provided ) for the entire patient population , but patients with TD spent significantly less time on hospice than patients without TD ( 6 vs . 11 days ; RR = 0.49 ; 95 % CI 0.44-0.54 ; p < 0.0001 ). Transfusion-dependent patients were 38 percent more likely to receive hospice services for less than three days ( 27 % vs . 19 %; RR = 1.8 ; 95 % CI 1.26-1.52 ; p < 0.0001 ). These relationships remained similar in patients with acute and chronic leukemias ( p > 0.05 ).

The findings “ indicate that the need for transfusion support may significantly delay hospice enrollment ,” the authors concluded . “ Because use of hospice services is associated with lower use of resources and costs at EOL , allowing palliative transfusions for patients with terminal leukemia may maximize the benefits of hospice from both patients ’ and society ’ s perspective .”

These results support the notion of Medicare adding reimbursement for transfusion in hospice , which would mean fewer patients would have to choose between receiving palliative care and receiving transfusions , Dr . Olszewski explained . “ While hospice use in leukemias appears to be increasing , a large proportion of patients still die in the hospital ,” he added . “ Hospice care increases the likelihood of dying at home , where most Americans say they prefer to be at the EOL .”

Study limitations include variance in the data collected in the SEER database . The authors also did not collect information on cause of death .

The authors report financial relationships with Celgene , AstraZeneca , and Boehringer Ingelheim . The study was supported by a research grant from the American Cancer Society .

REFERENCE

Olszewski AJ , Egan PC , LeBlanc TW . Transfusion dependence and use of hospice among Medicare beneficiaries with leukemia . Abstract # 277 . Presented at the 2017 ASH Annual Meeting , December 9 , 2017 ; Atlanta , GA .

46 ASH Clinical News January 2018