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Table 2. Treatment exposure and modifications. Treatment exposure and modifications
Cycles given, number, median (range) Received full induction (6 cycles), % Received maintenance (> 6 cycles), %
Percentage of planned dosea <75%
75%-90%
90%-110%
110%-125%
Dose modification Yes
Type of modificationb Dose reduction Dose interruption Dose increase
Number of days of interruption if any,
median (range)
All patients (n=33)
4 (1-22) 9 (27.3%) 6 (18.2%)
3 (9.1%) 4 (12.1%) 25 (75.8%) 1 (3.0%)
20 (60.6%)
2 (10.0%) 18 (90.0%) 3 (15.0%) 4 (1 – 28)
Ruxolitinib in advanced relapsed/refractory HL
Patients’ exposure to the study drug
The median number of ruxolitinib cycles administered was four (range, 1 to 12) (Table 2). Nine patients received all six of the planned cycles of ruxolitinib and six of these patients continued on maintenance therapy with the JAK inhibitor. The remainder discontinued ruxolitinib therapy, most because of progressive disease and in one case due to adverse events.
Responses and outcomes
The patients’ disposition through the study is illustrated in Figure 1. Among the 33 HL patients included in the trial, one patient did not complete the first cycle of treatment because of progressive disease and was not, therefore, included in the efficacy analysis. At the end of the ruxoli- tinib induction period (6 months) three of 32 patients had a response, for an ORR of 9.4% (90% CI: 2.6-22.5%); the response in all three was partial. At some point during induction six of the 32 patients had a response, which was, in all six cases a partial response, for a best ORR of 18.8% (95% CI: 7.2-36.4%). A detailed analysis of the responders’ characteristics is provided in Table 3. Figures 2 and 3 illustrate metabolic evolution in two patients. Interestingly, UPN 611001, who had achieved a partial
response after six cycles of treatment, eventually entered complete remission during the follow-up, beyond the six cycles. Achievement of complete metabolic response was confirmed by central review. At the time of writing, two patients (UPN 611001 and 881001) are still taking ruxoli- tinib. Figure 4 illustrates changes in target tumor measure- ments in individual patients. The best reduction, if any, at any time throughout treatment is shown.
In addition, during the 6-month induction, transient sta- ble disease was recorded in 11 patients, albeit of limited duration. Overall, the disease control rate (including stable disease with complete and partial responses) was 53.1% (17/32 patients) (95% CI: 34.7-70.9%) with a median duration of 1.9 months.
The alleviating effect on systemic symptoms, such as pruritus, fever, and sweating, was noteworthy, starting within the first month of drug administration and com- monly lasting. The impact was most remarkable on the
Figure 1. Patients’ disposition. *N months on maintenance therapy: 4, 6, 6, 21, 16, 22; PD: progressive disease.
aDefined as follows: (total number of tablets taken/total expected number of tablets) *100, taking into account protocol-defined dose reduction. bThe total sum of the per- centages for the type and the reasons of modification may be greater than 100.0% as a patient may have had several types of modification and reasons for treatment mod- ification.
Table 3. Characteristics of responders (best response achieved during the 6-month ruxolitinib induction).
UPN
Prior treatment
Extranodal involvement
Liver
Breast
Liver, bone, lung
None
None
Lung
Response (Cheson 2007)20
PR*,1
PR
PR
PR
PR
PR1
611001 9
211004 8 601001 5 601004 5 641001 1
881001 5
ABVD, BEACOPP, MINE, IGEV, GVD, CAELYX, GVD, RT, BV
ABVD, RT, IVA, transplantation, MINE, GVD, BV, ASHAP
BEACOPP, DHAP, IGEV, transplantation-RT, BV
ABVD, DHAP, RT, RT, BV
ABVD2
ABVD, transplantation, MINE, BV, GEMOX
N
Type
*Patient eventually achieved a complete response during maintenance therapy. 1Patients still under treatment with ruxolitinib at the time of writing; 2Patient with morbid obesity not eligible for standard approaches with chemo/immunotherapy. UPN:unique patient number; RT: radiotherapy; BV: brentuximab vedotin; PR: partial response.
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