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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
`
`

`

`Nib/e 4. Parameters assocrated with response to TD.
`
`10
`
`Parameter percent
`
`Performance status
`0
`a l
`Light chain type
`it
`A
`
`Response
`
`P-value
`
`83
`37
`
`7]
`25
`
`0.002
`
`0.004
`
`993
`
`Tit/Me 5. Toxicity (WHO scale)
`
`Adverse effect
`
`Percent of patients (“/0
`
`Constipation
`Somnolencc and/or fatigue
`Mood changes
`Xcrostomia
`Tremor
`Peripheral neuropalhy
`Skin rash
`Headache
`Edema
`Vein thrombosis
`
`75
`57
`33
`34
`30
`23
`2|
`2|
`l7
`7
`
`Rib/e 6. Parameters associated with survn'al afterTD.
`
`Parameter
`
`Median survival (months)
`
`Povaluc
`
`Gender
`Female
`Male
`Disease status
`Primary refractory
`Refractory relapse
`Hemoglobin
`28.5 g/dl
`< 8.5 g/dl
`Performance status
`0
`2 l
`Light chain type
`R
`A
`Serum LDH
`< 220 lU/l
`> 220 lU/l
`
`Nut reached
`l2.6
`
`Nut reached
`9.6
`
`l3.0
`4.8
`
`l3.()
`6.6
`
`Not reached
`6.6
`
`13.0
`6.6
`
`0.05
`
`0 06
`
`0.0004
`
`0002
`
`0.004
`
`0.009
`
`anemia, and a decrease of previously elevated serum [32-
`microglobulin and LDH levels.
`Several variables such as gender, age. mycloma heavy
`and light chain type, hemoglobin. platelet count, serum
`LDH and BZ-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 < l00 x |0"/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
`
`00
`
`D
`
`~fir—-——-—1———'——g
`6
`n
`I.
`2.
`
`Martha
`
`Figure I. Overall survnval after treatment with thalidomide and desa-
`methasone.
`
`combination induced responses in 57% of patients who
`had previously received high dose therapy with stem cell
`support. The TD regimen was equally efi'ective in pa-
`tients with either primary resistant myeloma or with
`disease in resistant relapse; partial responses occurred
`in 60"" and 52% of patients respectively. Among all 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/or significantly 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 I or 2 on the WHO
`scale). The more common adverse 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 l0 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 I or 2
`leukopenia occurred in 4 patients. Thrombocytopenia
`or anemia that could be attributed to the treatment were
`not seen. The dose of thalidomide was escalated to the
`
`scheduled dose of 400 mg p.o. daily in 36 patients (82%).
`The average daily dose of thalidomide was 400 mg in 32
`patients, 300 mg in 3 patients and 200 mg in 9 patients.
`The median time to progression for all patients was
`
`Dr. Reddy’s Laborattxios, Inc. v. Celgene Corp.
`IPR2018—01509
`Exhiiit 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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