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`Dr. Reddy’s Laboratories, Inc. v. Celgene Corp.
`IPR2018-01509
`Exhibit 2024, Page 1
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`Dr. Reddy’s Laboratories, Inc. v. Celgene Corp.
`IPR2018-01509
`Exhibit 2024, Page 2
`
`
`
`Table 4. Parameters associated with response to TD,
`
`Parameter percent
`
`Performancestatus
`0
`a
`Light chain type
`k
`ve
`
`Response
`
`P-value
`
`83
`37
`
`73
`25
`
`0.002
`
`0.004
`
`Table 5, Toxicity (WHO scale)
`
`Adverse effect
`
`Percent ofpatients (%)
`
`Constipation
`Somnolence and/or fatigue
`Mood changes
`Xcrostomia
`Tremor
`Peripheral neuropathy
`Skin rash
`Headache
`Edema
`Vein thrombosis
`
`75
`57
`33
`34
`30
`23
`21
`21
`17
`7
`
`Table 6. Parameters associated with survival after TD.
`
`Parameter
`
`Median survival (months)
`
`P-value
`
`Gender
`Female
`Male
`Disease status
`Primary refractory
`Refractory relapse
`Hemoglobin
`28.5 g/d)
`<8.5 g/dl
`Performancestatus
`0
`>I
`Light chain type
`k
`a
`Serum LDH
`$220 1U/1
`>2201U/I
`
`Not reached
`12.6
`
`Notreached
`9.6
`
`13.0
`4.8
`
`13.0
`6.6
`
`Not reached
`6.6
`
`13.0
`6.6
`
`0.05
`
`0.06
`
`0.0004
`
`0.002
`
`0.004
`
`0.009
`
`anemia, and a decrease of previously elevated serum [2-
`microglobulin and LDH levels.
`Several variables such as gender, age, myeloma heavy
`and light chain type, hemoglobin, platelet count, serum
`LDH and B2-microglobulin, performance status, bone
`marrow plasmacytosis, disease status, prior high dose
`therapy and resistance to dexamethasone, were evaluated
`for their possible correlation with response to TD. Our
`combination induced responses in 40%of patients with
`thrombocytopenia(platelet count < 100 x 10°/dl) and in
`59% of patients without thrombocytopenia (P = 0.47).
`The TD regimen was active in 56%of patients whose
`disease was resistant to an immediate prior treatment
`which contained high dose dexamethasone. Also, our
`
`993
`
`Figure 1, Overall survaval after Weatment with thalidomide and dexa-
`methasone.
`
`combination induced responses in 57%of patients who
`had previously received high dose therapy with stemcell
`support. The TD regimen was equally effective in pa-
`tients with either primary resistant myeloma or with
`disease in resistant relapse; partial responses occurred
`in 60%and 52%of patients respectively. Amongall the
`variables tested for their possible association with re-
`sponse,light chain of lambda type and impaired perfor-
`mance status were associated with a lower probability of
`response toTD (Table 4).
`Furthermore, the TD regimen was administered to
`eight patients with primary refractory myeloma who were
`eligible for high-dose therapy with autologous stem cell
`support, but this procedure could not be performed due
`to extensive tumor load with heavily infiltrated bone
`marrow, thrombocytopenia and/orsignificantly impaired
`performance status. Four of such patients responded,
`blood stem cells were collected and subsequently the
`patients received high dose melphalan with autologous
`blood stem cells as a consolidation treatment.
`Side effects after treatment with TD are shown in
`Table 5. Most adverse effects were due to thalidomide
`and were mild or moderate (grade | or 2 on the WHO
`scale). The more commonadverse effects were constipa-
`tion, somnolence and fatigue. Approximately one-third
`of patients developed mood changes, xerostomia or
`tremor, Some degree of peripheral neuropathy occurred
`in 10 patients and this side effect necessitated interrup-
`tion of thalidomide in three patients. Maculopapular
`skin rash was not uncommon but it usually subsided
`with reduction of the dose of thalidomide. Deep vein
`thrombosis occurred in three patients. Grade | or 2
`leukopenia occurred in 4 patients. Thrombocytopenia
`or anemia that could be attributed to the treatment were
`not seen. The dose of thalidomide wasescalated to the
`scheduled dose of 400 mgp.o.daily in 36 patients (82%).
`The average daily dose of thalidomide was 400 mgin 32
`patients, 300 mg in 3 patients and 200 mgin 9 patients.
`The median time to progression for all patients was
`
`Dr. Reddy’s Laboratories, Inc. v. Celgene Corp.
`IPR2018-01509
`Exhibit 2024, Page 3
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`Dr. Reddy’s Laboratories, Inc. v. Celgene Corp.
`IPR2018-01509
`Exhibit 2024, Page 4
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`Dr. Reddy’s Laboratories, Inc. v. Celgene Corp.
`IPR2018-01509
`Exhibit 2024, Page 5
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