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• chronic myeloid leukemia ( CML ): 24 % ( n = 10,465 )

• multiple myeloma ( MM ): 22 % ( n = 9,605 )

• acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ): 2 % ( n = 1,052 )

• acute lymphocytic leukemia ( ALL ): < 1 % ( n = 403 )

• other hematologic malignancies : 6 % ( n = 2,711 )

Except for trials investigating treatments for CLL and AML / MDS , more than 50 percent of participants were < 65 years ( see TABLE 2 ).

“ We weren ’ t surprised to see that , overall , adults aged 75 years and older were underrepresented in clinical trials , as this is common across cancer trials ,” Dr . Kanapuru said , “ but we were surprised by the magnitude of the gap for this age group , particularly for CML trials .”

Nearly 80 percent of patients enrolled in trials for CML were younger than 65 years , while only 50 percent of patients diagnosed with CML from SEER data fell in that age group . Similarly , in the ALL trials , more than 85 percent of participants were younger than 65 years ( see TABLE 3 ).

The disparity grew larger among older patients : Those 75 years or older accounted for 29 percent of patients with CML , but

TABLE 2 . Age Distribution of Participants Enrolled in Trials for Hematologic Malignancies

TABLE 3 . Age Distribution of Trial Participants Compared With SEER Incidence

SEER = Surveillance , Epidemiology , and End Results

only 4 percent of trial participants .

Dr . Kanapuru also highlighted some encouraging insights from this analysis . Among patients aged 65 to 74 years , the proportion enrolled in lymphoma ( excluding CLL ) and CML trials essentially mirrored the reported incidence of blood cancers in this age group . In MM and CLL trials , the proportion enrolled in the 65 to 74 age group was higher than the reported incidence in this group . However , adults older than 75 years were still underrepresented in FDA clinical trials , despite the high number of diagnoses of incident hematologic cancers in this age group .

She noted that there are multiple barriers to enrolling older adults in clinical trials . For example , trial exclusion criteria often prohibit people with a history of previous cancers or comorbid or coexisting illnesses , which older adults are more likely to have , compared with younger individuals .

“ Doctors may hesitate to enroll these older patients because they aren ’ t sure how they will tolerate investigational medications ,” Dr . Kanapuru said , also citing the heterogeneity of the older population as a reason for their underrepresentation . “ You can have one 75-year-old who is healthy and another person of the same age who is frail and has a lot of coexisting illnesses ,” she said . Study limitations include its retrospective design and variance in the data collected in the SEER database .

The authors report no financial conflicts .

REFERENCE

Kanapuru B , Singh H , Myers A , et al . Enrollment of older adults in clinical trials evaluating patients with hematologic malignancies – The Food and Drug Administration ( FDA ) experience . Abstract # 861 . Presented at the 2017 American Society of Hematology Annual Meeting , December 11 , 2017 ; Atlanta , GA .

Corticosteroids are the guideline-recommended firstline therapy for adult patients with immune thrombocytopenia ( ITP ), but a recent clinical trial suggests that regulating thrombopoiesis with recombinant human thrombopoietin ( rhTPO ) could improve platelet production and restore immune tolerance in this population .

In a prospective , multicenter , randomized , controlled trial , investigators questioned whether high-dose dexamethasone and rhTPO would work synergistically to improve platelet response in adults with treatment-naïve ITP . At the 2017 ASH Annual Meeting , Miaomiao Wang , from the Department of Hematology at Qilu Hospital of Shandong University in Jinan , China , and colleagues reported that frontline combination treatment led to higher rates of platelet count restoration , compared with corticosteroids alone . The study enrolled 245 newly diagnosed , treatmentnaïve patients with ITP ( age range = 18-75 years ) between July 2013 and December 2016 from 25 centers in China . At the time of presentation , 196 patients had undergone randomization . One hundred people were assigned to receive high-dose dexamethasone with rhTPO and 96 to receive high-dose dexamethasone alone .

In both study arms , dexamethasone was given orally at 40 mg a day for four consecutive days . In patients whose disease did not respond , the four-day course of dexamethasone was repeated on days 11 to 14 .

In the experimental arm , patients received concomitant 300 U / kg rhTPO subcutaneously daily during the first 14 days . Treatment could be discontinued for patients with platelet counts that recovered to > 100 × 10 9 / L or who experienced an increase of > 50 × 10 9 / L from baseline platelet count . If participants had platelet counts drop to < 10 × 10 9 / L with active bleeding , use of rescue treatments such as platelet transfusion and hemostatic agents were allowed , at the discretion of the investigator .

Patients were assessed for early response at day 14 ( primary endpoint ), and study visits were scheduled monthly through the end of month six or until disease relapse . Response was defined as achieving a platelet count ≥30 × 10 9 / L and at least a two-fold increase of baseline platelet count and absence of bleeding ; complete response ( CR ) was defined as platelet count ≥100 × 10 9 / L .

At day 14 , patients in the combination group had a higher incidence of early response , including CRs , than patients in the high-dose dexamethasone monotherapy arm :

• any response : 89 vs . 64 ( 89.0 % vs . 66.7 %; p < 0.001 )

• CR : 75 vs . 41 ( 75 % vs . 42.7 %; p < 0.001 )

Responses were maintained through six months , the authors reported , and remained higher in the combination group :

• any response : 51 vs . 35 ( 51 % vs . 36.5 %; p = 0.022 )

• CRs : 46 vs . 31 ( 46.0 % vs . 32.3 %; p = 0.043 )

Though high-dose dexamethasone and rhTPO also outperformed high-dose dexamethasone monotherapy on the secondary endpoint of response duration ( p = 0.04 ), there were no differences between the groups for time in therapeutic range , bleeding scores , and use of rescue treatments .

There were also no significant differences in the incidence of treatment-related adverse events ( AEs ) between the two groups , the researchers observed . No patient tested positive for neutralizing antibodies against TPO . Three patients had grade ≥4 AEs in the combination group , including early cerebral hemorrhage ( n = 2 ) and cerebral infarction ( n = 1 ). One patient died because of early cerebral hemorrhage ; none of these events were deemed treatmentrelated . No patient tested positive for neutralizing antibodies against TPO .

“ Our findings suggest that the addition of rhTPO to high-dose dexamethasone is superior to high-dose dexamethasone monotherapy in the treatment of newly diagnosed treatment-naïve adult [ patients with ] ITP ,” the researchers concluded . “ Thus , this combination can be a feasible frontline therapy in [ this patient population ].”

The use of investigator ’ s decision to guide rescue treatment may have introduced bias and limited the study ’ s findings .

The authors report no financial conflicts .

REFERENCE

Wang M , Qin P , Zhou F , et al . Recombinant human thrombopoietin ( rhTPO ) and high-dose dexamethasone ( HD-DXM ) versus high-dose dexamethasone monotherapy as frontline treatment in newly diagnosed adult immune thrombocytopenia ( ITO ): a prospective , multicenter , randomized controlled trial . Abstract # 13 . Presented at the 2017 American Society of Hematology Annual Meeting , December 9 , 2017 ; Atlanta , GA .

56 ASH Clinical News February 2018